Tuesday, October 13, 2015

II. Is Theoretical Biology Hiding A Critical Flaw In Selection Theory Proper? “Molecular Selection” Is A Crack In The Foundation. Is Molecular Selection just pseudo-science?

This discussion is follow-up to a prior post, and is pertinent to my lead theories ‘Virtual Closed Systems’ (Does Life Violate The Second Law? Implications of Virtual Closed Systems, and ‘Indifferent Time’, as well as other discussions that I have initiated on my blog site. I note for reference my discussion of R. Pascall’s paper (2013) on Kinetic Stability Theory, as further relevant to basic questions about the validity of “molecular selection” as chemistry, and as meeting qualifications of scientific research, i.e. basic feasibility at a theoretical or experimental level. It begs the question, as to why this kind of “research” is valid for publication in so called “peer reviewed” magazines. I have already presented evidence, both theoretical and experimental, that such nonsensical science is no better than “perpetual energy”.  These are not perpetual energy devices, but are claims of self-organizing, self-ordering matter, matter which they allege oppose laws of diffusion and heat-dissipation (fundamental to chemistry), and are equally dubious, and forbidden by the second law, as well as the first- as they are made without a single positive experiment or without any definition of what such a theory is in terms of how it would be disproven or negated. There are the absence of any test criteria or even a defined hypothesis. Yet these “molecular selection” and “maximal flow” theories, apparently, continue to be flogged in peer reviewed magazines. Ironically, unlike bogus perpetual energy claims, these theories as “molecular selection” get a free ride in the magazines, openly, with no resistance whatsoever from the scientific community. That does a great disservice to science, to those who adhere to scientific principals, and to the fair, pursuit of science now, and in the future.  In other words, such pseudoscience promoted as “peer reviewed” does great harm which cannot be quantified. The reason I bring up these points is that they conflict with my lead theories, and that is the purpose of this discussion, and the reason I shall continue to bring up the errors shown in current papers relevant to Virtual Closed Systems theory and Indifferent Time.

*If the reader does not have the time to read this entire article I would strongly suggest you skip to the section “NOTES” at the bottom. This where I dissect the supposed supportive references of molecular selection in detail.

The article I reference here appeared in Transactions A of the Royal Society Phil. Trans. R. Soc. A (2011) 369, 620–623 doi:10.1098/rsta.2010.0312 http://rsta.royalsocietypublishing.org/content/369/1936/620

I explore further into the enigma surrounding the so called “molecular selection” and find only more ‘nothingness’, a critical void of actual evidence to support it. Just more references from its proponents who claim to have observed it, or rather that someone else observed it and reported on it. And many of these cited in recent papers, “some of the first observations of (molecular selection)” like Mills (1968) or Spiegelman (1967) are almost 50 years ago. It is a term or at least the concept that it embodies, that I’ve recently encountered in a number of locations, and heard it utilized first hand as an explanation for molecular behavior. Molecular selection has a number of aliases, self-organization, molecular evolution, and the like, but is also now a foundation of so called ‘molecular paleobiology,’ Fournier G. et al. (2015) http://www.ncbi.nlm.nih.gov/pubmed/25791872.

To start off, perhaps it should be noted that in the article itself, de Duve references his previous work of virtually the same title but almost two decades earlier: “Vital Dust: Life As Cosmic Imperative” (Vital Books, NY 1995). de Duve also cites three of his other works in his short review article, these are:

de Duve C. (1991) Blueprint for a cell: the nature and origin of life (Neil Patterson Publishers, Burlington, NC).

de Duve C. (2002) Life evolving: molecules, mind, and meaning (Oxford University Press, New York, NY).

de Duve C. 2005 Singularities: landmarks on the pathways of life. New York, NY Cambridge University Press doi:10.1017/CBO9780511614736 (doi:10.1017/CBO9780511614736)CrossRef

On first “blush” it would almost appear as though de Duve has simply re-published a scientific article here from his book, published almost two decades prior. Does this qualify as new research for a published scientific article? Apparently it does qualify , and de Duve explains:

“The title of this essay appeared, but without the question mark, as the subtitle of my book Vital Dust [1]. In that book and in others [2–4], I defended the view that life is an obligatory manifestation of matter, written into the fabric of the universe, and that there must be many sites of life, perhaps even intelligent life sometimes, in many parts of our galaxy and in others..”

Biologists like de Duve are clearly aware that their theory involving a chemical first or “bottom up” approach to the origins of life would likely involve a great number of chemical optimization steps:

“The conclusion emerging from this summary analysis is that the origin of Earth life, being dependent on deterministic chemical reactions and on frequently optimizing selection processes, must have been close to obligatory under the physical–chemical conditions that obtained at the site of its birth. This contention is further supported by the fact that a very large number of steps must have been involved.”

By “very large number of steps must have been involved” we can presume that de Sousa and other proponents, are essentially claiming that the chemical development of life, the precursor reactions, must have been numerous, i.e. involving numerous reaction steps. And so their theory asserts that life is a chemical reaction product, albeit a product that had an extremely low probability of occurance.

Furthermore, the next part of the same paragraph strongly suggests that de Duve, like other biologists, is fully aware of the argument that a series of low probability events would, (S1…S2…S3…) if required to occur in succession of each other, lead to a very unlikely probability of the final event, as per normal probabilistic calculations would provide:

“For the final outcome to have a reasonable chance of taking place, most of those steps must have had a ‘reasonably high probability’ ([12], p. 1034) of occurring. Otherwise, the probability of the entire succession ever coming to fruition tends to become vanishingly small [1,12].”

So, returning to the theoretical issues: what would be the probability of a series of theoretical chemical steps, which lead up to a complex molecule such as the first RNA? If some steps (1-3) leading to a molecule were to occur only by chance alone, this would roughly be calculated as the p(molecule occurring) = p(step 1) * p(step 2) * p(step 3) and so on, but with each probability the frequency, or probability of its occurrence decreases. The probability multiplies again, when we attempt to envision getting three of those molecules, all by chance. This raises the fraction by a power of 3, making it even less likely an event, particularly if the fraction of molecules ever achieving unlikely conformations, let alone remaining stable in solution, becomes very remote if not theoretically prohibitive. And so the claim that RNA or some precursor molecule came about exclusively by chance “roll of the dice” is highly problematic since it may involve many possible reactions or side reactions, but moreover, these are more theoretical equilibriums, reactions that one can’t show normally in chemistry because they are energetically disfavored. So it may be surprising, to some, that this doesn’t sound at all like chemistry. But given the vanishingly low probability, and the lack of steps with “reasonable high probability” it should be surprising that this chemical pathway is considered feasible at all? No reasonable, high probability steps are ever described. The purely probabilistic “mechanism” we have just outlined here, has nothing to do with chemistry proper, it is not relevant to mechanism; and in fact, assumes no mechanism as such an assumption would mean that probability itself , chance, was not the factor. (the probability of obtaining “heads” five times in a row, by simple probability, isn’t calculable if there is higher probability of heads due to some mechanical aberration.) The argument that chemistry involves species reacting in more probable situations with more probable reactive species, is not the same argument. [It is in fact, the “propagating chemistry” I discuss HERE that I discuss as an alternative description of the pre-life or pre-RNA chemistry they propose to self-assemble. The reason is that the theoretical products they propose, to propagate and by chance, interact in one reaction after another, again by chance, defies the second law, as solutions do not behave in this way. Each microstate is reacting and reaching a lower energy state simultaneously.] Furthermore, in my view, the central assumption of their argument that there is a finite probability of a reaction should be in question, as we find no physical examples of this in nature. None on the bench. Their entire model of chemistry does not hold true even in the most elementary bench chemical model. Their model of using chance or probability is misrepresentative, since chemical reactions are actually highly probable, not improbable. Otherwise chemistry would not be such a precise science. The certainty by which these microstates reach their products, precludes the notion that it is not certain, or has opened the door to “other chemistry” they imply, i.e. the self-propagating chemistry of their model.

Nature does not advance by “mistake.” The idea that a flood or storm occurred randomly is not the same as the mechanics behind the storm, which did not impart a force by chance. And simply because molecules may end up with other molecules in solution by chance, does not mean that the reaction itself is driven by chance, by probability. So one has to consider thermodynamics of what is driving the chemical reaction itself. It has to be a chemical reaction. And yet a chemical reaction would involve certain reaction pathways, i.e. S1…S2…S3 and so on, as well as the loss of useful energy, but this obviates a purely chance scenario. The chance” dictated by the 2nd law of thermodynamics preempts their model of self-propagating chemistry in this case. Chemistry is mechanism driven, in theory. It is the model of the hypothesis in question here, the framework, (not the specifics of what those reactions actually are) since we should have doubts (based on their lack of providing any chemical examples) that it’s even clear what it should be. We realize that the question of “a chance of RNA” forming from n molecules, is a distinct question from “what are the species or precursor reactions leading up to RNA?” those are independent issues of one another. And I would argue, there is no substantive basis to claim a reaction will occur if you cannot name what those individual reaction components are. Otherwise, we could make all kinds of ridiculous predictions, Pb could turn to Au for example, “by chance, even despite it’s highly astronomically low frequency” and that claim is not permitted.

There is also a chance, the bio-physicists will tell us that entropy (an event N) may proceed in the opposite direction that it is favored, though extremely slight, and I explore HERE. That’s the thinking of statistical mechanics with respect to this problem. But the biologists and bio-physicists are likely keenly aware that there’s a bigger problem, and that’s the thermodynamic barrier. RNA is much more organized, and is a unique molecule, never found on asteroids or meteors. It isn’t lying around, and that’s because it has been manufactured by an intelligent organism, already containing DNA. To get around this dilemma, I believe that’s why they argue so vehemently for the ability of matter to self-organize, and for some kind of alleged “natural molecular selection” to be this force which can bridge the thermodynamic divide, and help physics run in a direction it isn’t meant to, if only for a short time. If you’re reasonably going to pursue that theory, you have to weigh probability of many theoretical events, and it gets very remote when these are stacked together, so selection is supposed to operate here. Which brings us back to our discussion…about improbability of those steps S1,S2,S3…n occurring! It has seemed relatively “easy” for biologists to say “an organism will outcompete or eat a lesser organism, and thus a more “evolved” complex organism will survive, but it’s not at all easy to envision that with inanimate chemistry, with molecules. So this is, in my opinion a theater in which the self-selection theory can be looked at very carefully, and if looked at too closely, it is found to be grossly lacking in substance or evidence to support its basic feasibility, that would be a single chemical experiment. Let us not raise the bar too high. A single step from S1 to S2 showing a reversal in the tendency of the second law would suffice to demonstrate this. Recall the statement that by de Sousa and others, that there is “chemistry before selection”. Yes where, how and when? I and other practitioners would be more than interested to see such evidence of self-selecting molecules, but the fact that such chemistry would have many useful implications to drug research also has a flip side- such claims in this arena would need to be shown as distinct from the myriad other chemistries already known. The obvious question that I raise here and elsewhere (see comment I made in Quanta https://www.quantamagazine.org/20140122-a-new-physics-theory-of-life/ is that it is theory, a theory of chemistry, and yet there is no chemical reaction for us to examine, not even in theory. But let us return again to the probabilistic argument i.e for dissipative theory, the basis of their theory, an example with links here https://www.quantamagazine.org/20140122-a-new-physics-theory-of-life/.

What de Sousa must also realize is that this same argument , i.e. the increasing improbability of a final event, gained by a series of highly unlikely events, applies to selection theory- not only for its alleged implications for bio-chemistry, but for selection theory in general. However, what is very different about this reference of de Sousa’s, or rather the context in which natural selection is discussed, is that it is specifically regarding hypothetical environments, chemical steps, which are not known. I don’t believe that it fully resolves this issue. de Sousa means for the context of chemical natural selection to be not that different from so called Darwinian Natural Selection, and in fact teaches that molecules may be selected for in much the same way as Darwinian Natural selection  implies as he states in the same paper:

“Originally formulated by Darwin as the mechanism of evolution of reproducing living organisms, natural selection also affects replicating molecules such as RNA, as first shown by Spiegelman [7]…. and since repeated in a variety of ways by many investigators. In both cases, the essence of the process lies in the imperfections of reproduction. For all sorts of reasons, whenever entities are replicated, variants of the original model are inevitably produced. Selection acts on those variants to automatically bring out those that are most stable and, especially, most capable of producing progeny, under the prevailing conditions. This process is inseparable from replication itself and must have appeared at the same time as the first replicating molecules in the development of life. “

The notion that life might be driven by what is “most stable” shows a very striking misunderstanding of the chemistry underlying biological systems. Many drugs cause their toxicities on bioorganisms for this very reason, because they are the most stable binding to a specific site, or energetically stable configuration, i.e with organism’s DNA, or an enzyme , which is more stabily binding to the natural molecule. Furthermore, many examples of more stable formations are highly toxic to life, precipitation of water (ice) is a lower energy form of water, but also the binding of metals to organism’enzymes, Pb, Hg, and other toxic metals are only toxic because they bind more strongly, than the more biologically desirable Ca or Mg ions.  These thought experiments verify to us that the arrangments of living chemistries are not the most stable that are possible, but the stability is resisted. How? By infusion of energy by the organism. Consumption of energy prevents water from freezing inside the cells, or tissues, it keeps chemical gradients from reaching stable states. It is absurd to believe that it is a function of a mere chemical reaction, even in theory, since the energy component, is missing from their description. (These are factors I address in my theory of VCS and elsewhere, in “indifferent time”.) They have omitted the energy argument completely in “chemical selection”, and have ignored the opposing forces , diffusion, exothermic drivers, and unavailability of free energy, that oppose the very chemistry they propose.

Many are aware that similar arguments have been made against natural selection theory, for a number of years at a theoretical if not mathematical level.  (For example, those regarding the mathematical improbability of successive improbable events i.e mutations in some tens of thousands of genes leading to positive forward progress), BUT it is also well known these arguments have been rejected vehemently by the core of evolutionary biology.

That it is not rejected here, but is in fact embraced as a feasible mechanism, makes this admonition somewhat more surprising. If de Sousa had made such an indictment of natural selection theory, in the non-chemical sense and in the normal contexts of Darwinian Evolution or New Synthesis, i.e. that natural selection of organisms allegedly operates by similar if not analogous mechanisms that de Sousa himself discusses here and elsewhere, it would be outright rejected as blasphemy against New Synthesis. In fact such views likely would not see the light of day” in terms of peer-reviewed publications. But the important aspect of this reference is that it clearly shows that evolutionary biologists are fully aware that natural selection theory has the same basic weaknesses as chemical natural selection.

Why the willingness to openly discuss the mathematical improbabilities here in the case of chemical selection?” The clear articulation of the theoretical issue of natural selection from a mathematical perspective, the multiplication of probabilities” shows a keen awareness that this SHOULD be a very critical issue in natural selection theory proper. Here, a biologist clearly illustrates the very mathematical probability issue that is denied as being irrelevant elsewhere. Does this show that evo biologists are avoiding the discussion of contrary theoretical evidence? Barring molecular sex, that is, the hypothetical sexual selection of one “attractive” molecule for another sexy molecule, what are we to make of this in terms of the selection theory? Let us review the quote: “…Otherwise, the probability of the entire succession ever coming to fruition tends to become vanishingly small” Would de Sousa agree that the probability that a theoretical series of chance mutations (which are indifferent) also leads to events in organisms i.e. forward “progress” would be viewed as “vanishingly small?”  

What still remains to be understood, are highly ambiguous (if not pseudoscientific) statements such as: 
“Additional evidence for [molecular selection] is provided by the growing number of instances of evolutionary convergence ….There are reasons to believe that molecular selection may similarly come close to optimization under sufficiently stringent constraints…”
in the article that are statements allegedly, about physical phenomenon, completely without supporting chemical evidence or citation. Again, it is impossible for us to determine what chemically, “evolutionary convergence” might mean, let alone “evolution” in terms of chemistry. Does water evolve? How about NaCl? If we are to believe for even a moment that this “chemical selection” is based in science, these chemical distinctions must be made clear by de Sousa and others of the “chemical evolution.” They must provide clear examples of what reactions are chemical evolution and which are not. That is the problem with evaluating any of their examples, such as nucleic acid chemistry. They fail to realize that nucleic acids are merely polymers, no different than the chemistry governing their monomers, these are the ubiquitous rules governing chemistry. The formation of DNA complex, though much more complex than simple atoms, is in principal energetically following the same rules as any other chemical process in inanimate systems). Such terms as “molecular selection”, “optimization” and “sufficiently stringent constraints” have no physical meaning in chemistry or are not defined by the authors of these kinds of claims, (i.e. where is a reaction NOT optimized?) but yet are cited repeatedly and with emphasis by their peers in other publications as fact. And as I have demonstrated here, the “optimization” of chemical processes, at least non-manipulated, natural ones, tend towards disorder and lower energy, but not with less available free energy than they had before, but essentially, the same unavailable energy they had before. So they purport to discuss chemical theoretical processes that are entirely imbalanced in their energy. And as I’ve commented elsewhere in another essay, the molecular selectionists purport to describe a kind of “perpetual energy mechanics”, alleged processes that generate more freely available energy than they consume. The claims of “molecular selection” are as vacuous and shaky in their evidence as they are in their definitions. What reasons are there specifically, to believe that “molecular selection” is a bona fide physical phenomenon, meaning one that is actually different than any other chemistry involving molecular species? Or, that there is anything resembling “optimization” in natural chemistry? They must realize that “optimizing” could imply that their chemistry they propose, in theory whatever it may be, will not ever occur as it is more “optimal” for it not to. It is tiresome that they continue to wave their hands with nucleic acid experiments, which are known to behave within the laws sof chemistry that are applicable to all other molecules, and make certain claims without specifying why a particular nucleic acid is unique, i.e. “evolving”. The term “optimize” imbues the inanimate chemistry with properties it does not have. What we do know, but what molecular selection proponents fail to acknowledge, is that the optimization of all inanimate chemical reactions favors products with less energy and energy of a form that is less available to do work, not the opposite. de Sousa’s argument in this paper to equate molecular selection principals with natural selection theory in general, i.e., Darwinian selection, I believe raises new and important theoretical questions about selection theory in general. But more importantly, it fails to address the problem of “chemistry before natural selection” as it cannot account for imbalance in available energy, a problem that my new theory of VCS, specifically addresses.

Addendum: (September 25,15) When I present my case to reviewers for a new molecular species, say one that is releasing high nitric oxide levels, I must present a reaction that involves two species A and B and give justification for why those species will combine. These are fundamental to chemistry. Furthermore, I must typically provide evidence of a product of A and B, and not just A-B but presumably one that will release another by-product, NO. That means that I now have presented both theoretical and empirical evidence. The proponents of “molecular selection” intend for us to believe that they have evidence of propogative reactions leading to simple nucleic acids. Nucleic acids are far too complex a product , to be used as “evidence” for their chemical arugment, and they have not examples of this in nature (outside of those made my organisms). So, their burden instead, should be to provide evidence of a much more simpler reaction, which gives a product that then drives another. The question that I ask of this theoretical reaction they provide, is thus: does this reaction oppose forces in solution? Does it oppose diffusion, or of its own dissipation of energy, terminating in a few steps? If they insist on maintaining their exemplary reaction is some kind of nucleic acid I pose the same problem(s) for that reaction as well. It is identical. There is no evidence that they provide here and yet it is published by various peer reviewed publiications as though it is factual based chemistry. These publications have not been held accountable fairly, to the same rules that are applicable to other scientists working in chemistry.




(*The so called molecular seletion or “molecular evolution’ is chemistry that is proposed without doing experimental controls or basic verification done in chemistry

Regarding the primary reference de Sousa quotes, recall one of de Sousa’s central arguments: “Originally formulated by Darwin….natural selection also affects replicating molecules such as RNA, as first shown by Spiegelman [7]”

I looked specifically at the citation, the key one, that is apparently cited by de Sousa as evidentiary for “molecular selection”. If you look at a similar Spiegelman and Mills paper, of the exact same year, which deals with in vitro RNA, and RNA viruses, you will find that these are neither self-replicative molecules, nor are they replicating in natural environments, that is, without assistance of RNA enzymes extracted from an organism. There is absolutely no evidence to conclude that reaction of these inanimate molecules will improve their odds of reacting further in “successive” steps as proposed by molecular selection proponents. This is a better reference to Spiegelman’s key work, and others (see below), investigating, “natural selection” and also so called environmental selection of the molecules of interest, which are RNA and also enzymes which process RNA in vitro.






It is interesting that de Sousa and others have chosen these references for support of molecular selection, as there are much better examples of the exact experiment Spiegelman and Mills performed, and these are well known in a process called PCR invented by Kary Mullis. Spiegelman states in his paper:


The availability of a molecule which has discarded large and unnecessary segments provides an object with obvious experimental advantages for the analysis of many aspects of the replicative process.”


That might have been inspiring to Spiegelman and Mills back in 1967, but it is not in any way showing how RNA is “discarding large and unnecessary segments”. Unnecessary to whom? Furthermore, it is hardly showing Darwinian natural selection” as de Sousa claims it to be, and further, it is a gross misinterpretation or at worse, a reading into, artificial non-real desires or wants of molecules which don’t exist. And simply because it is in print, in a cited reference ( citation=^170) doesn’t change these facts. It is well known that small products of DNA are faster replicating than larger kb sized strands, owing to the processing speed of the thermal stable polymerase, typically TAQ polymerase. In fact it is well known that smaller lengths consume nucleotides far better than longer DNA segments, an effect known as “noise” or non-specific binding and one that DNA researchers attempt to avoid. I could say much more about this, but what is relevant is that the reference is not what de Sousa and others claim it to be. That is a fact. And simply because Spiegelman invoked the words “natural selection” and believed with certainty that he’d found evidence” for RNA segments, “discarding” unnecessary segments, he was obviously reading into molecules, artificial wants or desires that do not physically exist. If de Sousa really meant this to be a reference supporting the “first demonstration” of self-replication, he’s truly traversing himself here. The main gist of Speigelman appears to be taken out of context by de Sousa, an investigation into how RNA virus operate, not to show self-replication, AND critically, it is with RNA and enzymes which process RNA. So it is yet another primary reference which does not support or define “molecular selection” experimentally, at least not in a non-teleological sense. The evidence we have for replicating RNA would give no support for de Sousa’s statement that molecules “desire optimization” or that some non-chemical phenomenon as chemical selection is occurring in molecular broths in the sea, or hydrothermal vents or anywhere else..(see the paragraph where de Sousa states “additional evidence…” above). What you will find however, if de Sousa is willing to cite these references, is that RNA and the enzymes that process RNA, do not exist or function outside the test tube for long. Why is that? Let us do a thought experiment. Let us put large quantities of highly active DNA or RNA along with enzymes, into a large vat of chemical amino acids and salts. After a time t (sufficient), will we find the DNA or enzyme to be HIGHER in order? That is, more reactive than it was at t=0? Consider that molecules in free communication with adjacent molecules react with these, and reduce their energy with a variety of irreversible chemical processes. What we expect to find is that the molecules did select other species, but these are lower energy species, to effectively dissipate stored energy or potential energy. In fact, there is no evidence to lead us to believe that any other chemistry is expected. This basic experiment would directly refute their claim of self-order would it not? It’s merely an example of the kind of experiment that they should run as a control, and explain why and how, their chemisty is or would be any different. And it’s the exact question I would suspect that de Sousa and others who support the delusion and pervasive myth surrounding “molecular selection”, would not want to answer.



  1. http://www.weizmann.ac.il/complex/tlusty/courses/landmark/Speigelman1967.pdf
  2. In Vitro Analysis of Self Replicating Molecule, S Spiegelman 1967 http://www.jstor.org/stable/27836918?seq=1#page_scan_tab_contents


  1. Fournier GP1, Alm EJ. (2015) Ancestral Reconstruction of a Pre-LUCA Aminoacyl-tRNA Synthetase Ancestor Supports the Late Addition of Trp to the Genetic Code. J Mol Evol. pr;80(3-4):171-85. doi: 10.1007/s00239-015-9672-1. Epub 2015 Mar 20.

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