­­­­­Given that the archive system does not preserve the attached files, I include herewith the whole text of the NY Lecture

Best--Pedro

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New Year Essay for FIS

*Reflections on Evolution Theory. J. S. Torday*

1. *BRIEF CRITICISM of Current Evolution Theory***


When I think of evolutionary biology I think of Paul Gauguin’s painting“Where Do We Come From? What Are We? Where Are We Going <https://r.search.yahoo.com/_ylt=AwrT6VvsKjRaox8AFGMPxQt.;_ylu=X3oDMTEyMWVmNzJpBGNvbG8DZ3ExBHBvcwMxBHZ0aWQDQjQ5ODFfMQRzZWMDc3I-/RV=2/RE=1513397100/RO=10/RU=https%3a%2f%2fen.wikipedia.org%2fwiki%2fWhere_Do_We_Come_From%253F_What_Are_We%253F_Where_Are_We_Going%253F/RK=2/RS=61chECAD2IhvlKlXb8ri3l3xT8M->”. These questions arise from time to time. In a sense, Darwin’s reply was to free us from The Great Chain of Being, only to leave us in limbo with metaphors like random mutation and Natural Selection, which are scientifically untestable and unrefutable. I seriously began addressing this problem about 20 years ago, having come across a new addition to the Modern Synthesis, the application of developmental biology to evolution theory, or EvoDevo. Thinking that the evolutionists had discovered the kind of science being done by me and my peers on the cell-cell communication mechanisms that mediate embryogenesis. Only to find that _there is literally no cell biology in evolution theory*^1 *_. This gap in the Evolutionary Biology literature is apparently the result of a historic glitch, the evolutionists relinquishing the work being done by Haeckel (‘Ontogeny Recapitulates Phylogeny’) and Spemann (‘Organizer’ hypothesis) at the end of the 19^th Century for want of mechanisms for these concepts that would advance the field of Evolutionary Biology. Instead, the evolutionists embraced genetics as their means of promoting evolution science. **

In retrospect, that was an unfortunate decision since embryogenesis is the only mechanism we know of that generates form and function, which is the essence of evolutionary change. But the mechanism of embryogenesis through growth factor signaling between cells would have to wait until the mid-20^th Century. Having made one of the original observations in support of cell-cell signaling and lung development, after 50 years of investigation we had assembled a working model of lung alveolar structure and function in 2007 *^2 *, employing dynamic space-time mechanisms of cell-cell signaling necessary for alveolar formation and function. Such a deep, transcendent perspective on the origins of biologic gas-exchange, referring all the way back to the cellular adaptation to gravity, begged the question as to how and why this mechanism evolved. So I decided to apply what I knew about lung development, phylogeny and pathophysiology at the cellular-molecular level as a means of deconvoluting lung evolution *^3 *.

**

*2.**EPIGENESIS: new findings***

Such musings about the cellular origins of the organ of gas-exchange were further advanced by the discovery in our laboratory that the cause of childhood asthma was epigenetic *^4 *. Exposure of pregnant rats to nicotine, the biologically active ingredient in cigarette smoke that causes asthma, could induce this disease molecularly, cellularly and phenotypically for at least three generations, opening up to new ideas about how organisms directly inherit genetic traits from their environment, as first suggested by Jean-Baptiste Lamarck in the 18^th Century. The prospect of epigenetic inheritance being a major effector of evolution gave rise to a novel way of thinking about evolution, not as the Darwinian merging of gene pools for reproduction, but as a heritable change in DNA readout, particularly with reference to The First Principles of Physiology- negentropy, chemiosmosis and homeostasis-homeorhesis- that emerged from the cellular approach to the mechanism of evolutionary adaptation. Again, because there is such a breadth and depth of knowledge of lung biology across species in combination with lung pathobiology, it became apparent that there was a causal relationship between geochemical changes during the Earth’s history and their affects on the evolution of gas-exchange, reinforcing the idea that evolution was non-random and that the forces of evolution were those of Nature- gravity, gases, ions, heavy metals. By reducing the phenotypes of development and phylogeny to their cellular-molecular elements in relationship to what was occurring in the environment, a narrative for evolution could be formed *^5 *.

*3. EPIGENESIS: its evolutionary significance *

For example, recent data on the history of oxygen levels in the atmosphere have made it apparent that they have not gone up gradually, but have gone up and down fairly dramatically, varying between 15 and 35% over the last 500 million years. The effects of hyperoxia fostering giant organisms have been known for a long time, but no one had considered the concomitant consequences of hypoxia, the most potent natural effector of physiology known. The effects of alternating hyperoxia and hypoxia gave way to an evolutionary understanding of the advent of endothermy/homeothermy *^6 *, and to insights to consciousness that diverged from various dogmas of biology.

A recent breakthrough in transcending descriptive biology is the recognition of the critical importance of epigenetic inheritance in the evolutionary process and its crucial role in reproduction. Indeed, mammalian reproduction is critically dependent upon several endoviral endogenizations. Lewis Wolpert *^7 * has stated that “It is not birth, death or marriage, but gastrulation which is truly the most important time in your life”, gastrulation being the stage of embryogenesis during which the mesodermal germ layer is formed, dictating the further development of the fetus through interactions between the mesoderm, endoderm and ectoderm. It is now known that the genes that control the transition from the blastula to the gastrula undergo epigenetic modifications, offering a mechanistic basis for understanding how such epigenetic marks affect embryogenesis. Therefore, the local environment largely determines the immediate impact of epigenetic inheritance that is limited and edited during meiosis, and then again during morphogenesis as a derivative of the unicellular state. Therefore, the zygotic unicellular state must be properly appreciated as the crucial intermediary in the modulation of these epigenetic influences, not merely because that phase lies between, but as the embodiment of the reiteratively-elaborated eukaryotic organism. The obligatory return to the unicellular stage through sexual reproduction is the controlled process that permits that crucial re-centering and modulation of both the Epigenome and the intrinsic genome. It is this recapitulation through the zygotic unicell with its unique capacities that can account for both the remarkable stability over time of many species and the phenotypic plasticity of others, something that cannot be readily accommodated by a random mutation/selection Darwinian model.

Indeed, the proper perspective for the extent of the influence of the zygotic unicell is to look beyond the alluring structure and function of multicellular organisms and instead accept that eukaryotic organisms have never actually left their unicellular state—the myriad permutations and combinations that Francois Jacob referred to as “tinkering” *^8 * are merely ways in which the dominant unicell has flexibly adapted to an ever-changing environment. It is as if the unicellular state delegates its progeny to interact with the environment as agents, collecting data to inform the recapitulating unicell of ecological changes that are occurring. Through the acquisition and filtering of epigenetic marks via meiosis, fertilization, and embryogenesis, even on into adulthood, where the endocrine system dictates the length and depth of the stages of the life cycle, now known to be under epigenetic control, the unicell remains in effective synchrony with environmental changes.

4. *TWO ENDS: one for biologists, the other for physicists *

The powerof the cellular-molecular approach has revealed itself by gaining insight to the long-sought mechanistic relationship between physics and biology. As mentioned above, the reduction of lung evolution to the unicellular state was a consequence of the realization that the adaptation to varying levels of oxygen in the atmosphere was accommodated by the physical chemistry of the cell, initially by the insertion of cholesterol into the cell membrane of unicellular eukaryotes, our forebears, and subsequently through cell-cell interactions that mediate the production of lung surfactant, the evolved functional state of cholesterol in the gas-exchanger of multicellular organisms.

As a result of the internal consistency of the cellular molecular mechanisms that mediate gas-exchange by the lung, both developmentally and phylogenetically, the mechanistic basis for the well-recognized pre-adaptations/exaptations were traced back to the novel concept for The First Principles of Physiology in the protocell. The utilization of cholesterol delivered by the frozen snowball asteroids that pelted the atmosphereless Earth to form the oceans spontaneously formed micelles, primitive cell-like spheres composed of semipermeable lipid membranes. Insight to that mechanism was derived from the synthesis of cholesterol when the oxygen levels on Earth were great enough to provide the 11 atoms of oxygen needed to synthesize one molecule of cholesterol. Or what the discoverer of the cholesterol synthetic pathway, Konrad Bloch, referred to as a ‘molecular fossil’. Importantly, lipids also exhibit hysteresis, or ‘molecular memory’, which is essential for evolution so that the organism ‘remembers’ its biologic past in order to mount a response to environmental stress.

With the assembly of these ‘pieces’ of the evolutionary puzzle, it was realized that there were homologies between The First Principles of Physiology and Quantum Mechanics. The Pauli Exclusion Principle is homologous with the First Principles of Physiology; the ambiguity generated by the micelle, with its internal negative entropy and external positive entropy accommodated the Heisenberg Uncertainty Principle; and the non-localization of particles in the Cosmos is homologous with the pleiotropic distribution of genes within the organism, as is the formation of electrochemical fields due to the coherence of calcium waves resulting from the pleiotropic distribution of genes*^9 *. **

The basis for the interrelationships between physics and biology are likely due to their common origins in the Singularity/Big Bang, forming the Cosmos, and in the process generating the recoil due to Newton’s Third Law of Motion, i.e. that every action has an equal and opposite reaction. In the case of physics, the recoil of the Big Bang gave rise to balanced chemical reactions, whereas in the case of biology it fostered the self-referential, self-organizational basis for the cell. Thus, there is a mechanistically-based continuum encompassing the Singularity/Big Bang, physics and biology, the aggregate of which is what we think of as consciousness.

**

*References Cited***

1. Smocovitis V. Unifying Biology. Princeton, Princeton University
   Press, 1996.

**

2. Torday JS, Rehan VK. Developmental cell/molecular biologic approach
   to the etiology and treatment of bronchopulmonary dysplasia. Pediatr
   Res. 2007 Jul;62(1):2-7.**

**

3. Torday JS, Rehan VK. The evolutionary continuum from lung
   development to homeostasis and repair. Am J Physiol Lung Cell Mol
   Physiol. 2007 Mar;292(3):L608-11.**

**

4. Rehan VK, Liu J, Sakurai R, Torday JS. Perinatal nicotine-induced
   transgenerational asthma. Am J Physiol Lung Cell Mol Physiol. 2013
   Oct 1;305(7):L501-7.**

**

5. Torday JS, Rehan VK. Evolutionary Biology, Cell-Cell Communication
   and Complex Disease. Wiley, 2012.**

**

6. Torday JS. A central theory of biology. Med Hypotheses. 2015
   Jul;85(1):49-57.**

**

7. Vicente, C. An interview with Lewis Wolpert. Development 2015 Aug
   1;142(15):2547-8.**

**

8. Jacob, F. Evolution and tinkering. Science 1977 **Jun
   10;196(4295):1161-6.**

**

9. Torday JS. Quantum mechanics predicts evolutionary biology. Progr
   Biophys Mol Biol (in press).**


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Pedro C. Marijuán
Grupo de Bioinformación / Bioinformation Group
Instituto Aragonés de Ciencias de la Salud
Centro de Investigación Biomédica de Aragón (CIBA)
Avda. San Juan Bosco, 13, planta 0
50009 Zaragoza, Spain
Tfno. +34 976 71 3526 (& 6818)
pcmarijuan.i...@aragon.es
http://sites.google.com/site/pedrocmarijuan/
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