Some Principles of Causal Analysis in Genetics (1936)


high frequency radiation and particles of high velocity are very important components of the environment, causing heritable changes by a process called mutation. Even if we could conduct our experiments behind 30 metres of lead the fact that mutation has a temperature coefficient is enough to show that it depends in part on energy fluctuations which are uncontrollable.

Mutations must be controlled. See also: Life on Earth – Flow of Energy and Entropy


The concept of negative entropy (first introduced by E. Schrodinger – ref [2]) or information (Shannon – ref [20]) and the ability of the Biosphere to effectively extract it from the Sun’s radiation is very important for life on Earth.

My comment: Haldane bastardized Darwin’s theory via use of Hugo de Vries definition of “mutation” before Schrodinger commented on an obvious fact. Schrodinger considered the anti-entropic energy of the sun to be a source of information. Information about the epigenetic landscape is linked to the physical landscape of DNA via nutrient-dependent RNA-mediated events and cell type differentiation in all genera.  A recently published journal article links the anti-entropic epigenetic effect of the sun’s biological energy to the controlled design of a membrane that is required for photosynthesis. See:

IM30 triggers membrane fusion in cyanobacteria and chloroplasts


A central role of IM30 in triggering membrane fusion explains the various pleiotropic functions ascribed to IM30 in the past, mainly based on studies using higher plants, algae or cyanobacteria with decreased IM30 contents. Lipid transport24,44, vesicle budding or fission19, protein translocation and insertion29,45,46, membrane modification28,47, as well as biogenesis of photosystems21,30,48 have been ascribed to IM30.
My comment: The biogenesis of photosystems can now be compared to claims that link abiogenesis to their evolution. Biogenesis was reported as:

Fusion protein controls design of photosynthesis platform

Excerpt: The study elucidating the role of IM30 involved biologists, chemists, biochemists, and biophysicists…

My comments: Any elucidation of facts that link the sun’s biological energy from the de novo creation of light-induced amino acids to the creation of proteins and the membrane that enables the biophysically constrained chemistry of photosynthesis must involve biologists, chemists, biochemists, and biophysicists. Otherwise, the link from RNA-directed DNA methylation and RNA-mediated amino acid substitutions to cell type differentiation in all cells of all individuals of all genera may be lost in the reporting of results from different disciplines or different research groups.

Taken separately, the findings from separate disciplines and different research groups led one cosmologist to complain “…you are continually confusing physicists with biologists. The article is about physics, not biology.”

The article was: Is cosmology having a creative crisis?


The Big Bang is a story about entropy.

My comment: Entropy cannot be linked to the biological basis of life without the anti-entropic epigenetic effects of the sun. Nevertheless, I bowed out of the discussion after an apology. Clearly, the differences between most physicists and most biologists are insurmountable. Physicists cannot seem to communicate across disciplines and explain the interactions among metabolic networks and genetic networks. To them, and to many evolutionary biologists and most human ethologists, the biggest question about biologically-based cause and effect is likely to be “What about birds?”

Biology to a Physicist

Dobzhansky (1964) alluded to this problem with the question about birds in Biology, molecular and organismic. He wrote:

…the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!”

Then he added a caveat.

Such pronunciamentos can be dismissed as merely ridiculous. They are, however, caricatures of opinions entertained by some intelligent and reasonable people, whose views deserve an honest and careful consideration and analysis. Science must cope with new problems that arise and devise new approaches to old problems. Some lines of research become less profitable and less exciting and others more so.”

Dobzhansky (1964) also noted that

Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.

Since then, the only productive lines of research have been less profitable than those pursued by researchers whose funding comes from the evolution industry and/or the big bang cosmology industry

See, for comparison: Top-down causation: an integrating theme within and across the sciences?

Abstract excerpt:

The idea of top-down causation is intimately related to concepts of emergence; indeed, it is a key factor in strong theories of emergence.

Article conclusion:

…the papers in this Theme Issue largely are explanatory of known aspects of science—that is, they are post hoc explanations. What is crucially needed is predictions of new tests that will confirm the hypothesis that top-down causation is real, and not just an epiphenomenon. The papers by Jaeger (microbiology) and Noble (physiology) are strong steps forward in this regard. This is perhaps the area where most needs to be done, across the board in all domains. Areas where striking progress is being made in this regard are epigenetics [22] and social neuroscience [23]. These papers are in fact dealing with top-down causation: the way they provide experimental confirmation of this concept needs to be made more explicit.

My comment: The idea that the Big Bang story about entropy could be linked to the emergence of life or to any aspect of life via the papers by Jaeger (microbiology) and Noble (physiology) in the context of top-down causation via an amino acid substitution or anything else that might differentiate the cell types of all genera is absurd. Simply put, the Big Bang cosmology industry has failed to link biologically-based cause and effect from the sun’s biological energy to life on earth and to the biodiversity of morphological phenotypes and behavioral phentypes.

For comparison, the ability of biologists, chemists, biochemists, and biophysicists to link a fusion protein to the creation of the membrane that constrains the chemistry of photosynthesis links their ability to

1) start with the de novo creation of light-induced amino acids, and link it to

2) the amino acids substitutions in proteins that determine the cell types of all individuals of all genera via the physiology of reproduction.

Successful reproduction enables the fixation of the energy required for cell type replication in organized genomes. Cells and species need energy to survive. Mutations perturb protein folding, which prevents the most successful use of energy. That’s how mutations are linked to pathology.

Haldane and others linked mutations to evolution, which explains why biologists, chemists, biochemists, and biophysicists have had a difficult time Combating Evolution to Fight Disease.


Molecular biology and evolutionary biology have been separate disciplines and scientific cultures: The former is mechanistic and focused on molecules; the latter is theoretical and focused on populations. However, these domains are beginning to converge in laboratories addressing molecular mechanisms that explain how evolutionary processes work, and bring these processes to bear on medical problems such as cancer and infectious disease. Each discipline can be viewed as a missing link in the other’s description of biology, and in medicine.

My comment: Focus on theory and populations has contributed very little to what is known about the conserved molecular mechanisms of biologically-based cause and effect.

See this excerpt from my 4 published comments on Combating Evolution to Fight Disease

Darwin probably anticipated the insemination of population genetics that led to the bastardization of his detailed observations in the “Modern Synthesis.” He politely insisted that ‘conditions of life’ be considered before natural selection.

In our 1996 Hormones and Behavior review we linked Darwin’s nutrient-dependent ‘conditions of life’ to RNA-mediated cell type differentiation in species from microbes to man via their pheromone-controlled physiology of reproduction. See our section on molecular epigenetics in From Fertilization to Adult Sexual Behavior. We did not specifically mention the role of nutrients, but in subsequent works, I linked our model — as have others — to the hormone-organized and hormone-activated nutrient-dependent behaviors of other species.

Understanding that behaviors do not emerge in the context of mutations is crucial to the understanding of biologically-based cause and effect that links the epigenetic landscape to the physical landscape of DNA via cell type differentiation in all cells of all individuals of all genera. Caveat, there may be exceptions if species somehow emerge outside the context of everything currently known about the biophysically constrained chemistry of RNA-mediated protein folding.

If an emerged species if found, its emergence should be studied. Until then, serious scientists have guidelines that can be incorporated into their studies of biologically-based cause and effect that has been linked to the brain and human behavior. See for example: Comparative approaches in evolutionary psychology: molecular neuroscience meets the mind

Abstract Excerpt:

Claims regarding evolved, uniquely human, psychological constructs should be constrained by the rigorous evidentiary standards that are routine in other sciences.

See also:

Understanding and accounting for relational context is critical for social neuroscience

In the comments on this article (free registration is required), I wrote:

New data on how genetic predispositions are epigenetically linked to phenotypically distinct neuroanatomy and behaviors is provided in the honeybee model. Across-species comparisons from insects to vertebrates clearly show that the epigenetic influence of food odors and pheromones continues throughout the life of organisms that collectively survive whereas individuals do not. These comparisons also attest to the relative salience of sensory input from the rearing environment. For example, when viewed from the consistency of animal models and conditioned behaviors, food odors are obviously more important to food selection than is our visual perception of food. Animal models affirm that food odor makes food either appealing or unappealing. Animal models reaffirm that it is the pheromones of other animals that makes them either appealing or unappealing.

Socioaffective neuroscience and psychology may progress more quickly by keeping these apparent facts in mind: Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000).”

— Kohl, JV (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors Socioaffective Neuroscience & Psychology 2012; 2: 17338 – DOI: 10.3402/snp.v2i0.17338

Login to the “Frontiers” site and see the comments by George Ellis:

This is absolutely correct and forms part of the larger concept that top-down causation is a key factor not just in the way the brain works but in broader contexts in biology and even physics….

See also:

George Ellis: Great links, thanks. I’m intrigued by your work on pheromones. It is just possible it might relate to the issue of primordial emotional systems…

My comment: George Ellis is the co-author of Affective Neuronal Selection: The Nature of the Primordial Emotion Systems, which is an excellent review of what we detailed in our 1996 Hormones and Behavior review article. That invited review led to more details in another invited review that was published in 2001 as Human pheromones: integrating neuroendocrinology and ethology.  My group’s 2001 invited review won the same award for linking neuroendocrinology and ethology that Jack Panksepp’s group won in 2002 for publication of Comparative approaches in evolutionary psychology: molecular neuroscience meets the mind

George FR Ellis appears to understand the links from physics  to the biophysically constrained chemistry of nutrient-dependent RNA-mediated amino acid substitutions. He may also understand the link from protein folding to the primordial emotional systems of flies. However, he has made it clear to me that he does not want to discuss that link. For contrast:

Flies appear to have primordial emotional systems: See: Study reveals fruit flies exhibit the building blocks of emotion.


we put forth the view that emotions are a type of internal brain state with certain general properties that can exist independently of subjective, conscious feelings, which can only be studied in humans

My comment: Their view is placed into the context of an experiment that linked visual stimuli designed to mimic an overhead predator to induction of a persistent and scalable internal state of defensive arousal in flies. That keeps people focused on what they have been taught to believe is a link from visual stimuli to behavior. The results can also be placed into the context of population genetics that link the nutrient-dependent pheromone-controlled ecological adaptation of insects to human behavior.

The behavior of all genera obviously arises in the context of ecological variation. Ecological variation in the supply of nutrient energy that links all morphological and behavioral phenotypes to all others via the conserved molecular mechanisms studied by biologists, chemists, biochemists, and biophysicists. Only evolutionary theorists and Big Bang cosmologists continue to place studies by serious scientists into the context of ridiculous theories that link mutations to evolution without linking the sun’s biological energy to nutrient availability. Theoretical physicists and evolutionary theorists skip from emergence to evolution with no links at all to biologically-based cause and effect. That’s why their theories must change, like the weather.

For example, serious scientists now know:

Your DNA changes with the seasons, just like the weather.

The outside of the spools are coated in molecules called methyl markers. Under certain conditions, the methyl markers flag a gene, and the section will uncoil. That gene is now exposed to messenger RNA, which picks up the code and begins the process of making proteins.

Changes in DNA with the weather do not seem to link mutations to anything except pathology. Excess sun exposure is now linked to skin cancer, for example. But see: Vitamin B3 and DNA repair. Other experimental evidence of biologically-based cause and effect also links nutrient-dependent RNA-directed DNA methylation to DNA repair from the balance of viral microRNAs and nutrient-dependent microRNAs. The balance limits virus-driven entropic elasticity and genomic entropy. For example, RNA-mediated amino acid substitutions repair DNA.

DNA repair mechanisms are linked from the de novo creation of light-induced amino acids to the RNA-mediated amino acid substitutions that stabilize nutrient-dependent protein folding in all genera during life history transitions that link the physiology of reproduction to the fixation of beneficial amino acid substitutions. The anti-entropic epigenetic effect of nutrient-dependent microRNAs control the entropic elasticity caused by viral microRNAs.

The nutrient-dependent microRNAs typically seem to prevent the viral microRNAs from causing the perturbed protein folding that links viruses to pathology. The microRNAs, for example, are responsible for RNA-mediated DNA repair and healthy longevity in the absence of nutrient stress and or social stress that virus-driven immune system changes use to contribute to diseases that are manifested during the life histories of species from honeybees to humans.

See also: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.


The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, diseases of the X chromosome, learning and memory, as well as conditioned responses to sensory stimuli (Kohl, 2012).

Evolutionary theorists and theoretical physicists have no model organism and no model of how the Big Bang story about entropy becomes a story about ecological variation that leads to ecological adaptation via the biophysically constrained RNA-mediated chemistry of nutrient-dependent protein folding in all genera. Without a model, theorists have only their stories.

See: Scientific method: Defend the integrity of physics


The imprimatur of science should be awarded only to a theory that is testable. Only then can we defend science from attack.

Revisit this claim from Panksepp et al (2002)

Claims regarding evolved, uniquely human, psychological constructs should be constrained by the rigorous evidentiary standards that are routine in other sciences.

See also: Bacteriophages isolated from chicken meat and the horizontal transfer of antimicrobial resistance genes, which was reported as:

Phage spread antibiotic resistance


nearly half of the 50 chicken meat samples purchased from supermarkets, street markets, and butchers in Austria contained viruses that are capable of transferring antibiotic resistance genes from one bacterium to another—or from one species to another.

My comment: This links viruses and viral microRNAs from entropic elasticity to cell type differentiation via nutrient-dependent microRNAs that repair DNA damage. That is how microRNAs link the epigenetic landscape to the physical landscape of DNA via RNA-directed DNA methylation and RNA-mediated amino acid substitutions that stabilize the organized genomes of all genera.

Anyone who was taught to believe in the pseudoscientific nonsense about mutations that lead to antibiotic resistance will probably need to re-educate themselves and learn to accept biological facts that link ecological variation to ecological adaptations. Accepting ridiculous theories is no longer an option for anyone who wishes to maintain any scientific credibility.

If, instead, viruses initially got their genes from their hosts, the de novo creation of amino acids and the creation of the membrane that enables the biophysically constrained chemistry of photosynthesis and RNA-mediated cell type differentiation in all genera could have been perturbed by the ingestion of animals by other animals. A difference of a few amino acids in plant viruses and animal viruses might be all that was required to link viral microRNAs to perturbed protein folding and pathology in every generation of every animal species that ingested the cells of another animal species. That’s food for thought, literally.

In the context of thoughts about food, it is interesting to note that some researchers have been examining the link from viruses to cell type differentiation for several decades. See for example:

Gene Silencing without DNA: RNA-Mediated Cross-Protection between Viruses (1999)

The DNA-binding properties of polyomavirus large T antigen are altered by ATP and other nucleotides (1991)

See also: A dynamic evolutionary and functional landscape of plant phased small interfering RNA (May 16, 2015)

The fact that some researchers are only now beginning to understand the the links from viruses to RNA-mediated gene silencing and cell type differentiation attests to the power of evolutionists and big bang cosmologists to keep the focus on their ridiculous theories. Their theories continue to kill millions of people each year who die needlessly because the theorists have never learned how cell type differentiation occurs, which is why their ridiculous theorists do not address biologically-based cause and effect.

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