diseases-disorders

From Hydra to humans vs a Lakatosian research program

Imre Lakatos

Excerpt: “A Lakatosian research programme[8] is based on a hard core of theoretical assumptions that cannot be abandoned or altered without abandoning the programme altogether. More modest and specific theories that are formulated in order to explain evidence that threatens the ‘hard core’ are termed auxiliary hypotheses. Auxiliary hypotheses are considered expendable by the adherents of the research programme—they may be altered or abandoned as empirical discoveries require in order to ‘protect’ the ‘hard core’. Whereas Popper was generally read as hostile toward such ad hoc theoretical amendments, Lakatos argued that they can be progressive, i.e. productive, when they enhance the programme’s explanatory and/or predictive power, and that they are at least permissible until some better system of theories is devised and the research programme is replaced entirely. The difference between a progressive and a degenerative research programme lies, for Lakatos, in whether the recent changes to its auxiliary hypotheses have achieved this greater explanatory/predictive power or whether they have been made simply out of the necessity of offering some response in the face of new and troublesome evidence.”
My comment: The so-called “Modern Synthesis” has no explanatory and/or predictive power. Recent changes have removed the hard core of theoretical assumptions, which once led to claims about random mutations that somehow were linked from natural selection to the evolution of increasing organismal complexity. New and troublesome evidence continues to attest to the need to remove neo-Darwinian theories from any further consideration whatsoever in the context of what is known about biologically-based cause and effect.
For example, “The origin of our body axes” is epigenetically linked via nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions to cell type differentiation via pheromone-controlled fixation of the amino acid substitutions and development of our central nervous system in this report: “In search of the origin of our brain
Science idiots must now link mutations to morphological phenotypes and to behavioral phenotypes during the development of biodiversity. They must start with asexual hydra and continue across all other species to primates.
Obviously, this will only be attempted by the biologically uninformed who will probably proclaim that the evolution of organismal complexity “just happens.” That’s what science journalist, Carl Zimmer left us with in his July 16, 2013 report on The Surprising Origins of Evolutionary Complexity.” “Others maintain that as random mutations arise, complexity emerges as a side effect, even without natural selection to help it along. Complexity, they say, is not purely the result of millions of years of fine-tuning through natural selection—the process that Richard Dawkins famously dubbed “the blind watchmaker.” To some extent, it just happens.”
Serious scientists continue to incorporate ridiculous theories in their reporting of results that refute the pseudoscientific nonsense of population geneticists. See: Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. They are forced to claim they don’t understand the involvement of RNA-binding proteins, amino acid substitutions, and thermodynamic cycles of protein biosynthesis and degradation that link metabolic networks via  RNA-mediated events to genes and the control of cell type differentiation.
Alternatively, maybe they don’t understand that Feedback loops link odor and pheromone signaling with reproduction via bio-physical constraints on the chemistry of protein folding and conserved molecular mechanisms of cell type differentiation in all cells of all organisms of all genera. Perhaps they should start with a literature review. For example: Signaling Crosstalk: Integrating Nutrient Availability and Sex
Excerpt:“The mechanism by which one signaling pathway regulates a second provides insight into how cells integrate multiple stimuli to produce a coordinated response.” It is that coordinated response that these researchers seem unable to explain even after they have linked the epigenetically-effected morphological and behavioral phenotypes of species from Hydra to humans.
My comment: This molecular epigenetics of this coordinated response were included in our 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior. Nothing known about cell type differentiation has changed since we wrote: “Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”
My comments to the Scientific American site: 
7/17/13 Darwin’s ‘conditions of life’ are nutrient-dependent. Nutrients metabolize to species specific pheromones that control reproduction in species from microbes to man via the same molecular mechanisms.
The epigenetic effects of food odors associated with nutrition and pheromones associated with socialization and with sexual reproduction are clearly responsible for linking the sensory environment directly to adaptive evolution sans consideration of mutation-driven evolution.
See for details: Nutrient-dependent/pheromone-controlled adaptive evolution: a model. Socioaffective Neuroscience & Psychology 2013, 3: 20553
The model includes examples of how a change in a single base pair results in an amino acid substitution that clearly links adaptive evolution, which has occurred during the past ~30,000 years in a human population in what is now central China, to the same molecular mechanisms in mice, other mammals, insects, nematodes, and microbes.
4/19/14 Ecological variation in nutrient availability and epigenetically-effected methylation is clearly the driver of ecological adaptations manifested in species diversity. If this had not already become clear to serious scientists, methylation would not be reported in the context of ‘Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan‘ (Instead, methylation is substituted for mutations and linked to epigenetic cause and effect.)
If nutrient-dependent pheromone-controlled ecological adaptations were not clearly responsible for species diversity, serious scientists might still claim that mutations somehow caused it, as they have claimed until recently. See: ‘A functional test of Neandertal and modern human mitochondrial targeting sequences. However, as serious scientists realized that there is no such thing as a fixed beneficial mutation, only evolutionary theorists continue to make claims based on the pseudoscience of population genetics.
It is unfortunate that pseudoscientists have influenced the ridiculous beliefs of so many people, because most of them can no longer grasp the scientific truth that life is nutrient-dependent and that the physiology of reproduction is controlled by pheromones in species from microbes to man. However, the fact that scientists like Svante Paabo have finally recognized the role of methylation is a sign that the next generation will be the one that dismisses mutation-initiated natural selection and/or mutation-driven evolution from any further consideration whatsoever.
Thus, there is still hope for scientific progress to be made by those who are not stuck with their opinions, while others examine the facts. See, for example, “Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems.”

terrarium-eco-system

In theory, or supported by experimental evidence?

Carl Zimmer typically makes statements like the one below without prefacing them with “in theory.” That’s how he establishes the bias towards evolutionary theory in nearly everything he reports.
For example: “During the development of eggs and sperm, each pair of chromosomes swaps pieces of their DNA. Over the generations, long stretches of DNA get broken into smaller ones, like a deck of cards repeatedly shuffled.
Inaccurate statements like that one make it appear that the evolution of biodiversity occurs across millions of years during which accumulated mutations somehow lead to fixed changes in the amino acid substitutions that differentiate the cell types of all cells in all individuals of all different species. Accurate representations of biologically-based cause and effect include RNA-mediated events, which link ecological variation to nutrient-dependent amino acid substitutions and chromosomal rearrangements.
The amino acid substitutions and chromosomal rearrangements occur in the absence of mutations that perturb protein folding. Instead, they help to ensure biodiversity via the metabolism of nutrients to species-specific pheromones. Pheromones control the physiology of reproduction in species from microbes to man, which is how they lead from nutrient-uptake to the control of biodiversity via conserved molecular mechanisms of cell type differentiation in all species.
The alternative that Zimmer and others like him continue to tout involves a ridiculous theory that accumulated mutations somehow lead to natural selection and the evolution of biodiversity. No experimental evidence of biologically-based cause and effect suggests that is possible. Furthermore, the amino acid-dependent protein folding that links the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man is biophysically-constrained. Simply put, that means the Laws of Physics prevent mutation-driven evolution by placing chemical ecology in a position that ensures what Darwin called his ‘conditions of life’ have been met. Minimally, his ‘conditions of life’ have always been nutrient-dependent, which is probably why evidence of RNA-mediated events clearly links nutrient uptake to ecological adaptations.
Until 1973, most evolutionary theorists could have excused themselves from intelligent conversations about the conserved molecular biology of amino acid substitutions and cell type differentiation. However, from the time that Dobzhansky stated his creationist perspective in the terms of evolutionary theory, it has become clearer that amino acids substitutions differentiate cell types in all species. In Nothing in Biology Makes Any Sense Except in the Light of Evolution, Dobzhanksy wrote: “…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.”
No experimental evidence of biologically-based cause and effect suggests the single amino acids substitutions that differentiate the cell types of these primates or the cell types of any other species can arise via a mutation or the accumulation of mutations. All experimental evidence and all model organisms that sexually reproduce via ligand-specific receptor-mediated fertilization exemplifies the fact that … exosomes are the carriers of a flow of information from somatic cells to gametes…That fact, like all other facts about sex differences in cell types indicates …that somatic RNA is transferred to sperm cells, which can therefore act as the final recipients of somatic cell-derived information.
Carl Zimmer is one of two people I know about who has written a book about viruses, see A Planet of Viruses. I’m not sure what planet his information came from, since it does not appear to include anything pertinent to links between the epigenetic landscape and the physical landscape of DNA in the organized genomes of species from microbes to man. However, a book published 2 years earlier by Luis Villarreal, see Origin of group identity: viruses, addiction and cooperation, includes the mention of pheromones 79 times.
Pheromones control the physiology of nutrient-dependent reproduction in living organisms via nutrient-dependent RNA-directed DNA methylation and RNA-mediated events that link amino acid substitutions to cell type differentiation via chromosomal rearrangements in all organisms. That’s why Zimmer’s book is of much less interest to me than Villarreal’s book.
Like his articles, Zimmer seems to be stuck touting evolutionary theory at a time when others have moved forward by providing experimental evidence of biologically based facts that link microbes to man via conserved molecular mechanisms, not via mutations and natural selection that Zimmer thinks is the basis for the evolution of biodiversity. Like Villarreal’s articles, those written by other serious scientists continue to attest to that fact that Carl Zimmer’s pseudoscientific nonsense will be exposed each time new experimental evidence is published that links RNA-mediated events to increasing organismal complexity with no mention of evolutionary events whatsoever.
See also: Body Cells Transfer Genetic Info Directly Into Sperm Cells, Amazing Study Finds.
Also, on July 31, 2013 Sayer Ji wrote: “Hereditary trauma: Inheritance of traumas and how they may be mediated”
Excerpt: “Mansuy and her team have succeeded in identifying a key component of these processes: short RNA molecules. These RNAs are synthetized from genetic information (DNA) by enzymes that read specific sections of the DNA (genes) and use them as template to produce corresponding RNAs. Other enzymes then trim these RNAs into mature forms. Cells naturally contain a large number of different short RNA molecules called microRNAs. They have regulatory functions, such as controlling how many copies of a particular protein are made.
See my comments on: Scientists unmask a piece in the puzzle of how the inheritance of traumas is mediated
1) “…traumatic stress alters the amount of several microRNAs in the blood, brain and sperm – while some microRNAs were produced in excess, others were lower than in the corresponding tissues or cells of control animals. These alterations resulted in misregulation of cellular processes normally controlled by these microRNAs.”
Nutrient stress and social stress act on the same central neuronal system that links epigenetic effects of food odors and social odors called pheromones on the microRNA/messenger RNA balance and cell type differentiation to mammalian behavior.
For details, see: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
The review follows from detailed representations with cross species examples of cause and effect in my 2013 published review and it adds the required details on the physics and chemistry of protein folding.
2) Kohl’s Laws of Biology: “The ecological origin of all biological laws is apparent 1) in the context of systems biology [91]; 2) in the context of the metabolism of nutrients by microbes [157]; and 3) in the context of how the metabolism of nutrients results in species-specific pheromones that control the physiology of reproduction [158]. Taken together, the systems biology of nutrient metabolism to species-specific pheromones, which control the physiology of reproduction, can be expressed in a summary of Kohl’s Laws of Biology: 1) Life is nutrient-dependent. See for review [2, 31]. The physiology of reproduction is pheromone-controlled. See for review [30]. In the context of nutrient-dependent epigenetically-effected human reproduction, it is clearer that the epigenetic effects of human pheromones integrate neuroendocrinology and behavior [104], which includes the neuroendocrinology of mammalian behavior associated with the development of sexual preferences [159].”
RNA-sequencing / exome sequencing now link RNA-mediated amino acid substitutions to cell type differentiation in all cells of all individuals of all organisms. Today’s news stresses the importance of RNA-mediated events to the understanding of differences between undifferentiated cancerous cell types and controlled cell type differentiation. New genome-editing technique enables rapid analysis of genes mutated in tumors. Simply put, researchers have applied what is known about RNA-mediated gene editing to help determine what goes wrong with cell metabolism processes in cancer cells. Why aren’t the theromodynamic cycles of protein biosynthesis and degradation limited by the biophysical constraints on protein folding that enable typical cell type differentiation via conserved molecular mechanisms in species from microbes to man? This rapid analysis of RNA-mediated genome editing eliminates the need for mouse models of what happens when genes are knocked out or knocked in. No need to wait for the mice to grow and manifest differences in their morphological and behavioral phenotypes as if mutations caused typical and atypical cell type differentiation as evolutionary theorist have told us occurs in the context of natural selection and the evolution of biodiversity.