Why Origin of Life research struggles to be taken seriously.

 Sunlight on the Puzzle of Prebiotic RNA?

Carl Linnaeus

In two previous articles for Evolution News (here and here) I have argued against the plausibility of generating biologically relevant polymers (proteins, RNA, and DNA) in a prebiotic world. Much of this argument was based on the requirement for homochirality of the building blocks and the precise chemical bonds necessary to achieve nucleotides for RNA and DNA. Admittedly, some scientists have proposed schemes that are more palatable to skeptics of origin of life (OOL) research. Therefore, here I will explain the positive steps that have recently been taken to solve the enigma of how RNA and DNA may conceivably arise in an abiotic world.

In my earlier article, discussing the discovery of uracil recovered from samples taken from an asteroid, I made clear that formation of RNA (or DNA) building blocks through linking ring-structured nucleobases (uracil, thymine, cytosine, adenine, guanine) to the ring-constrained back bone sugar ribose (or deoxyribose for DNA) is a hopeless abiotic endeavor. The chemistry needed to complete formation of the needed building blocks in high yield without the use of energetically charged substrates and enzymes (as living systems use) is untenable. Several OOL scientists have recognized this drawback. They have chosen a different path, considered below, to propose how biologically relevant nucleotides might have been produced chemically, using only starting compounds believed to be present prebiotically. 

Facile Synthesis of Pyrimidine Nucleosides (Cytidine and Uridine)

The chemical scheme envisaged employs a mechanism to build pyrimidine ring structures ab initio on ribose, rather than attempting to link them to this sugar. The entire synthetic process is as follows: 

Disparate reaction conditions in the multi-step syntheses (conditions are in bold text):

Step 1) Ribose + cyanamide / 0.2 M sodium carbonate (pH ~10), 55o C -> RAO

Step 2) RAO + cyanoacetylene / hydrosulfide in aqueous formamide, UV light -> Intermediates A

Step 3) Intermediates A / phosphate, anhydrous formamide, heat -> alpha & beta-ribopyrimidines (pyrimidine ribonucleosides completed)

Step 4) Intermediates A + 8-mercaptoadenine / dry state in magnesium chloride, 150o C -> Intermediates B

Step 5) Intermediates B / bisulfate in phosphate (pH 7), 60o C or sulfite in phosphate (pH 8-10), heat, UV light -> Intermediates C

Step 6) Intermediates C / nitrous acid (pH 4) -> adenine and inosine products (purine ribo- and deoxyribonucleosides completed)

The first step uses cyanamide, a compound likely present on the early Earth, to react with ribose in a two-step process that traps the 5-carbon sugar into the required furanose ring conformation.1 This putative RNA precursor, called ribo-aminooxazoline (RAO), now has the first three atoms destined to form the pyrimidine ring already attached to the appropriate carbon of ribose. It is noteworthy that ribose, competing against the other three possible 5-carbon sugars, is the preferential substrate in this reaction. From this point synthesis continues2 via step 2 in the table, using another simple abiotic prospect, cyanoacetylene, resulting in an intermediate that is readily converted to ribocytidine. Thus, in just three steps using simple reactants, the first nucleoside is nearly complete in fairly high yield. This product, however, needs to be in the beta configuration. But this is easily managed by exposure to UV light with a conversion rate as high as 74 percent. UV light also facilitates oxidation of cytosine to uracil (at much lower yield) completing the recipe for production of both pyrimidine nucleosides. The authors in the publication cited above describe an alternative route to uridine, offering some advantages in yield by performing the reaction with cyanoacetylene in the presence of hydrosulfide. 

Facile Synthesis of Purine [Deoxy]Nucleosides ([Deoxy]Adenosine and [Deoxy]Inosine)

To tackle the production of purine nucleotides, another putative chemical precursor feasibly present in an abiotic setting (step 4) is reacted in the presence of bisulfate with an intermediate in the alpha-ribocytidine pathway.3 Two isomers of beta-deoxyadenine (dA) result upon UV irradiation where the biologically relevant isomer exhibits yields close to 50 percent. Treatment of dA with nitrous acid gives partial conversion to beta-deoxyinosine (dI). Subsequent research by this group demonstrated the feasibility of producing the corresponding purine ribonucleosides (A and I) by carrying out the first reaction in alkaline sodium sulfite instead of bisulfate.4 The yields of the desired products are appreciably lower than those found for the pyrimidine products (10-40 percent vs 40-50 percent). In summary, these chemical synthetic studies under hypothetical prebiotic conditions have demonstrated respectable yields for the beta versions of ribo pyrimidines and purines as well as for beta versions of deoxyribo purines, representing the canonical building blocks used in biology.

The Homochirality Challenge

None of the studies indicated above differentiate between the two stereoisomers of ribose. Certainly, L-ribose should have been equally present with D-ribose in a prebiotic world, so RAO precursors would likewise be a racemic mixture. Another laboratory explored an innovative approach taking advantage of the fact that chiral molecules can align with a magnetic field due to spin states of all their electrons.5 Enantiomeric pairs of a compound will exhibit spin states aligning with opposing magnetic polarity. This principle is known as chiral-induced spin selectivity (CISS). Because magnetite is expected to be abundant in the sediment of bodies of water on the primordial Earth, it was hypothesized that Earth’s magnetic field would serve to magnetize the iron-containing sediment, providing a means to preferentially adsorb RAO enantiomers in different zones based on their CISS. The referenced experiments were performed in Petri dishes simulating this design, placing a magnet underneath the insoluble magnetite. The first round of selection eventually led to RAO crystallization on the magnetite surface, demonstrating a significant enrichment in either D- or L-RAO depending on magnetic polarity. 

After collecting the crystals, redissolving them in buffer, and repeating the magnetite-induced selection, the second round of crystallization resulted in optically pure RAO. From experiments like these it was proposed that homochirality of RAO could have been achieved on the prebiotic Earth where a small enantiomeric imbalance is induced within zones to retain preferentially one of the two RAO stereoisomers. With this occurring near shore, water flow redissolves the RAO crystals, followed by a subsequent dry phase when the shoreline recedes. When the water rises to this level again, RAO recrystallizes to a greater enantiomeric excess. That is since the magnetite had been conditionally enhanced magnetically in the previous round through the CISS effect.6 It was suggested that this repeated cycle of adsorption, crystallization, and spin-alignment on the magnetite surface may serve as a positive feedback loop, leading to the ultimate prize of crystalizing homochiral RAO.

Feasibility of This Chemistry Was Demonstrated, but Is It Plausible Under Prebiotic Conditions?

Considering first the proposal to attain homochirality of RAO, weak assumptions are required to accept this achievement. The authors noted that timing of crystallization is important. That is because if crystals are allowed to grow for too long a period of time, enantiomeric excess decreases and thus the chiral spin state training of magnetite is reduced or jeopardized. It would take a string of good fortune to have that cycle spontaneously repeated at the right length of time. It would also be expected that different zones along the shore would each select their own enantiomer of RAO.6 Despite having individual homochiral crystals, over larger areas the opposite stereoisomers are also crystallized. So how do they remain separated before and after undergoing subsequent reactions, leading to nucleoside synthesis? This can be readily accomplished in the laboratory, keeping crystals and their down-stream products isolated. But there is no guarantee they will remain isolated under abiotic situations.

Regarding the synthesis of nucleosides from RAO, several concerns come into play: 1) Multi-step syntheses diminish the yields of final products and increase probabilities of generating by-products that might compete for incorporation into RNA building blocks. The yields of purine nucleosides, in particular, suffer from the requirement for additional steps needed in their synthesis. 2) Most reactions require disparate conditions. How do the reactants in an abiotic environment become sequentially incorporated under these different reaction conditions (Steps 1-6)? In the laboratory this is self-explanatory, but it is not a trivial matter when chemistry is left to stochastic events. 3) Predictions of the chemical repertoire of a prebiotic Earth are largely unsubstantiated. Support for such predictions could potentially come from analyzing samples from other extraterrestrial bodies as was done with the asteroid Ryugu. Retrieval of samples from Mars would be a particularly exciting venue to explore. Without this type of confirmatory data our suppositions of prebiotic chemistry could simply be shooting in the dark. 4) The role of UV light is likely critical to the formation of these RNA building blocks. This can be a double-edged sword as UV light can also damage purines and pyrimidines by several means. 5) A prebiotic synthetic scheme leading to guanine has still not been elaborated. Instead, they propose that inosine, which is included in the schemes presented here, can substitute for guanine since it is able to base pair with cytosine (as guanine does). Inosine, however, is more akin to being a wildcard as it also base pairs with uracil and thymine. Such promiscuous base pairing will undoubtedly limit the functional gamut of RNA/DNA polymers and alter the structural dynamics that we now know are important for the biological roles of many RNAs.

Truly an Extraordinary Solution

I appreciate the quality of work that went into devising chemical schemes to synthesize purine and pyrimidine nucleobases, achieving the mandatory stereo and chemical specificity of furanosyl ribose established in living systems. This is truly an extraordinary solution using alleged prebiotic conditions. In my opinion, other attempts to meet this challenge have not come close to attaining such a level of accuracy. Unfortunately, the most significant problem is how this can be completed without a guided mechanism to direct each successive reaction and maintain respectable yields along the entire process. 

Beyond the initial synthesis of nucleic acid building blocks, there are more highly significant concerns once nucleotide chains have been assembled. Adjacent pyrimidines are very prone to form several types of chemical lesions elicited by UV light. Without a series of enzymes to repair such lesions, the repercussions for the damaged RNA/DNA molecule are poor. In current biological systems they result in mutations because of replication errors. Of course, in a prebiotic world repair enzymes would not exist. These concluding remarks shine light (pardon the pun) on future considerations of RNA/DNA polymers in a prebiotic world. If one wonders why origin-of-life science has its skeptics, unpretentious complications like those here reveal concerns and doubts that arise as we contemplate the field.

References

Springsteen G, Joyce GF. Selective derivatization and sequestration of ribose from a prebiotic mix. J Am Chem Soc 2004;126(31):9578-83 doi 10.1021/ja0483692.

Xu J, Tsanakopoulou M, Magnani CJ, Szabla R, Sponer JE, Sponer J, et al. A prebiotically plausible synthesis of pyrimidine beta-ribonucleosides and their phosphate derivatives involving photoanomerization. Nat Chem 2017;9(4):303-9 doi 10.1038/nchem.2664.

Xu J, Chmela V, Green NJ, Russell DA, Janicki MJ, Gora RW, et al. Selective prebiotic formation of RNA pyrimidine and DNA purine nucleosides. Nature 2020;582(7810):60-6 doi 10.1038/s41586-020-2330-9.

Xu J, Green NJ, Russell DA, Liu Z, Sutherland JD. Prebiotic Photochemical Coproduction of Purine Ribo- and Deoxyribonucleosides. J Am Chem Soc 2021;143(36):14482-6 doi 10.1021/jacs.1c07403.

Ozturk SF, Liu Z, Sutherland JD, Sasselov DD. Origin of biological homochirality by crystallization of an RNA precursor on a magnetic surface. Sci Adv 2023;9(23):eadg8274 doi 10.1126/sciadv.adg8274.

Ozturk SF, Bhowmick DK, Kapon Y, Sang Y, Kumar A, Paltiel Y, et al. Chirality-induced avalanche magnetization of magnetite by an RNA precursor. Nat Commun 2023;14(1):6351 doi 10.1038/s41467-023-42130-8.

"What could go wrong?"

 

Still yet more on why ID is already mainstream

 

Re:Norway's war on religious liberty.

 Diplomat magazine

By Willy Fautré, director of Human Rights Without Frontiers

HRWF (08.01.2024) – From 8 to 19 January 2024, the District Court of Oslo will examine the de-registration case of Jehovah’s Witnesses on the grounds of their exclusion policy of members, also named disfellowshipping.

The case follows the government’s denial of the Witnesses’ application for state grants in 2021, which they had received for 30 years. These subsidies are not “gifts” but allocations provided for by the Norwegian Constitution and laws to respect the principle of equality between religious communities, whatever their size, since the Church of Norway (Lutheran) is supported by taxpayers’ money.

A timeline in short

On 27 January 2022, the County Governor (Statsforvalteren) for Oslo and Viken, Ms. Valgerd Svarstad-Haugland, issued an administrative decision denying the state subsidy for the year 2021 to Jehovah’s Witnesses.

The starting point of the legal saga was a report addressed to the Ministry of Children and Family Affairs by Prof. Furuli, a professor emeritus of Semitic languages at the University of Oslo and a disfellowshipped Jehovah’s Witness himself, in connection with the exclusion and expulsion policy of members. The question was raised about how the report should be assessed with regard to the registration of and state subsidies to the Jehovah’s Witnesses.

Noteworthy is that Prof. Furuli supported a first decision in August 2021 by a Norwegian court “annulling” an ecclesiastical decision where the Jehovah’s Witnesses disfellowshipped one of their female members, Gry Helen Nygård. However, this decision was reversed on 9 July 2021 by the Borgarting Court of Appeal and on 3 May 2022 by the Supreme Court of Norway with a unanimous decision (5-0). Nygård then took her case to the European Court of Human Rights (ECHR), which rejected her complaint without giving any further reason, which is common when the ECHR regards complaints as clearly unfounded.

Nygård has also taken her case to a different court, the media, and has found a sympathetic ear from people hostile to Jehovah’s Witnesses.

On 25 October 2022, the County Governor of Oslo and Viken, Ms. Valgerd Svarstad-Haugland, demanded via letter that Jehovah’s Witnesses change their religious beliefs and practices, otherwise they would lose their registration. In her letter, she did not refer to any court decisions or complaints to the police, child welfare authorities, or other relevant authorities. The Witnesses proposed to meet her but she declined their request.

On 22 December 2022, the County Governor revoked their registration as a religious community.

On 30 December 2022, Oslo District Court granted Jehovah’s Witnesses a temporary injunction suspending the County Governor’s decision and pending litigation.

On 26 April 2023, the District Court lifted the injunction in response to a request by the Ministry of Children and Families. The decision was appealed.

On 30 June 2023, the Borgarting Court of Appeal dismissed the appeal on technical grounds.

What are and can be the consequences of the de-registration?

News reports about the State revoking the Witnesses’ registration stigmatize the nearly 12,000 Jehovah’s Witnesses of Norway.

The negative media coverage has led to considerable increase in verbal abuse, physical assaults, as well as vandalism of places of worship (e.g., offensive graffiti, arson).

The community is losing the State’s recognition of their religious marriages as well as some $1.6 million (USD) in government grants.

The State intrusion into the beliefs and practices of Jehovah’s Witnesses that is being examined in Norway can have a very negative impact on other religious communities in Norway and other countries.

The ruling against that religious community “can have consequences for a whole range of other faiths,” stated Dag Øistein Endsjø, professor of Religious studies at the University of Oslo, in an interview published in the newspaper Vårt Land .

In an editorial, Vebjørn Selbekk (editor-in-chief of the respected Norwegian Christian newspaper, Dagen) expressed fear that the County Governor may go on and sanction other religious groups whose beliefs and practices she happens to disagree with. He regarded the decision as anti-democratic, and expressed the hope that the Jehovah’s Witnesses will “emerge victorious from the upcoming court process.” Noteworthy is that Mr. Selbekk is not a Jehovah’s Witness and is critical of their theology.

Monsignor Torbjørn Olsen, the Secretary of the Catholic Norwegian Bishops’ Conference, wrote in a Norwegian media: “If the denial of registration stands, it may soon only be a matter of time before a number of other communities with ‘incorrect’ positions will be deregistered.”

Last but not least, a collateral damage is also the reaction of the Russian Ministry of Foreign Affairs whose spokesperson, Maria Zakharova, decried the hypocrisy of Norway which deregistered Jehovah’s Witnesses, while criticizing Moscow at international forums for banning that same religious community. She also added that Russia’s nationwide ban is hereby legitimized by the decision in Norway.

Psalms chapter 133 New World Translation study edition

 1.Look! How good and how pleasant it is

For brothers to dwell together in unity!+

 2 It is like fine oil poured on the head+

That runs down the beard,

Aaron’s beard,+

And runs down onto the collar of his garments.

 3 It is like the dew of Herʹmon+

That descends on the mountains of Zion.+

That is where JEHOVAH decreed his blessing

—Life everlasting

Some more post game analysis re: James Tour vs. the Sphinx.

 

The singularity is at hand?

 

Quantum neurology?

 Brain as a Quantum System: Theory Gets New Traction

Denyse O Leary

At New Scientist last week, George Musser talked about the way a theory of consciousness that sees the brain as a quantum system is now under reluctant consideration. Musser, author of Putting Ourselves Back in the Equation (Farrar, Straus and Giroux, 2023) went to visit anesthesiologist Stuart Hameroff, who — with theoretical physicist Roger Penrose — advances the quantum-based Orch Or Theory (orchestrated objective reduction of the quantum state).

Do Quantum Phenomena Create Conscious 

Experience?

Musser explains the basic idea of the Orch Or Theory (OOT), that conscious experience arises from quantum phenomena in the brain. The theory gained little traction in the past because it was difficult to test but Musser thinks that the use of anesthetics on brain organoids (picture above, they are lumps of brain tissue grown in a medium), along with other new methods, may enable the theory to be tested:

Such ideas have existed, in various guises, on the fringes of mainstream consciousness research for decades. They have never come in from the cold because, as their critics argue, there is no solid experimental evidence that quantum effects occur in the brain, never mind a clear idea of how they would give rise to consciousness. 

GEORGE MUSSER, “CAN QUANTUM HINTS IN THE BRAIN REVIVE A RADICAL CONSCIOUSNESS THEORY?”, NEW SCIENTIST, 17 JANUARY 2024

What, more specifically, is the Orch Or theory?

In short, it says that consciousness arises when gravitational instabilities in the fundamental structure of space-time collapse quantum wave functions in tiny structures called microtubules that are found inside neurons — and, in fact, in all complex cells.

MUSSER, ”RADICAL CONSCIOUSNESS THEORY?”

In quantum theory, a particle does not really exist as a tiny bit of matter located somewhere but rather as a cloud of probabilities. If observed, it collapses into the state in which it was observed. Penrose has postulated that “each time a quantum wave function collapses in this way in the brain, it gives rise to a moment of conscious experience.”

Hameroff has been studying proteins known as tubulins inside the microtubules of neurons. He postulates that “microtubules inside neurons could be exploiting quantum effects, somehow translating gravitationally induced wave function collapse into consciousness, as Penrose had suggested.” Thus was born a collaboration, though their seminal 1996 paper failed to gain much traction.

Of course, the Nineties was the decade of the Astonishing Hypothesis (Scribner, 1994), wherein Nobel laureate Francis Crick (1916–2004) proclaimed, “You’re nothing but a pack of neurons.” In those days, many thought that materialism had already won and no more sophisticated analysis was needed.

Quantum Processing in Bird Brains

Musser tells us that recent research suggests some kind of quantum processing does occur in the brain. One suggested example is the way a bird’s internal compass includes radicals with an “odd, unpaired electron”:

When these radicals eventually react, the outcome will depend on the strength and orientation of the magnetic field. The thinking is that the bird is sensitive to this in a way that allows it to tell north from south. The process is highly quantum as the radical pair electrons are entangled, which means that they act as a single quantum object, even though they are some distance apart.

MUSSER, ”RADICAL CONSCIOUSNESS THEORY?”

If that’s correct, we already know of at least one quantum process in a nervous system. Linking that up to human consciousness is still a stretch but, he says, scientists are more willing now to at least consider it.

And Other Research?

Musser seems to be on to something. In 2022, for example, researchers at Trinity College in Dublin did experiments that suggest our brains do quantum computation. They think that their finding may help solve a mystery:

Quantum brain processes could explain why we can still outperform supercomputers when it comes to unforeseen circumstances, decision making, or learning something new. Our experiments, performed only 50 meters away from the lecture theater where Schrödinger presented his famous thoughts about life, may shed light on the mysteries of biology, and on consciousness which scientifically is even harder to grasp.

TRINITY COLLEGE DUBLIN, “NEW RESEARCH SUGGESTS OUR BRAINS USE QUANTUM COMPUTATION,” PHYS.ORG, OCTOBER 19, 2022. THE PAPER IS OPEN ACCESS

Likewise, Dorje C. Brody, Professor of Mathematics at the University of Surrey, hopes that quantum processes can shed light on human behavior. For example, the order in which questions are asked is important in quantum physics but not in classical physics. But in that respect, the human mind often behaves more in a quantum way, he says:

For example, in a study published 20 years ago about the effects that question order has on respondents’ answers, subjects were asked whether they thought the previous US president, Bill Clinton, was honest. They were then asked if his vice president, Al Gore, seemed honest.

When the questions were delivered in this order, a respective 50% and 60% of respondents answered that they were honest. But when the researchers asked respondents about Gore first and then Clinton, a respective 68% and 60% responded that they were honest.

DORJE C. BRODY, “COULD QUANTUM PHYSICS BE THE KEY THAT UNLOCKS THE SECRETS OF HUMAN BEHAVIOUR?,” JANUARY 19, 2024

He sees the human response as more like a quantum system. 

How trying to understand human consciousness or behavior via quantum processes will work out is anyone’s guess. But here’s a prediction: It won’t help the cause of materialism much.