Sure, be glad to expand on my approach to evolutionary biology. I have
never bought in to random mutation and Natural Selection in principle, both
because as a developmental cell biologist, I know that mutations are not
readily incorporated into the gene pool; in fact just the opposite, they
cause still births and abortions. And Natural Selection is a metaphor, not
a mechanism, so how can it be tested experimentally. Furthermore, we know
that processes of evolution are reversible based on work by Jean Guex on
Ammonites, for example, showing empirically that such invertebrates were
impacted by environmental changes, causing them to revert to earlier stages
in their development and phylogeny, indicating that the processes that
generated the developmental/phylogenetic changes could not have been random
because there would be know 'trail' in a random event, so consequently
there must be some organizing principle(s) that determined those changes in
order to allow them to recapitulate the process. And work in my laboratory
has shown that chronic lung disease is actually 'reverse evolution' when
seen at the cellular-molecular level. What we see pathologically are
step-by-step reversal of the developmental and phylogenetic changes that
formed the alveoli of the lung under physiologic stress due to various
agents- mechanical, oxidative, bacterial. Just to be clear, I have made the
case for 'internal selection' through remodeling of structure and function.
Under stress to tissues they generate Radical Oxygen Species (ROS) due to
the shear force on the microvasculature....the cells involved in the
affected structure will mutate due to the production of the ROS, and
because of the prevailing homeostatic control, will remodel the
structure/function until they come up with a new cytoarchitecture that
doesn't produce ROS any longer....which is what we refer to as evolution
(hope that was clear.....it's also referred to as the Baldwin Effect).  As
for the First Principles of Physiology concept, based on the cell-cell
signaling mechanisms known to determine the development and phylogeny of
the lung, I was able to trace the process of alveolar evolution from the
swim bladder of fish forward to amphibians, reptiles, birds and mammals in
a step-wise fashion. From there, the trail becomes somewhat more difficult
to follow backwards because there hasn't been a systematic study of
organisms prior to vertebrates, assuming that their physiology wasn't
pertinent (WRONG), but we know that the skin is the most primitive organ of
gas exchange, so using knowledge of skin development and phylogeny offered
the means of tracing the gas exchange mechanism all the way back to the
unicellular cell membrane. That was achieved in large part by recognizing
the central importance of lipids throughout the process, starting with the
exploitation of cholesterol in the cell membranes of eukaryotes (organisms
with a nuclear membrane), our ancestors, facilitating gas exchange by
thinning out the cell membrane, culminating in the mammalian lung with the
use of cholesterol (and other lipids) to maintain the structure and
function of the alveolus by synthesizing and secreting lung surfactant into
the thin walled alveolar space, reducing surface tension, preventing
collapse of the alveolus upon exhalation (called atelectasis). As proof of
principle, if you delete the cholesterol synthetic mechanism from the
alveolar cells that make the lung surfactant, the embryonic lung
compensates by forming more of the connective tissue cells
(lipofibroblasts) that evolutionarily facilitated the evolution of the lung
from the swim bladder. As for the concept of First Principles of
Physiology- namely negative entropy (Free Energy), chemiosmosis (bioenergy
to sustain negative entropy) and homeostasis (to monitor the capacity of
the organism to adapt to an ever-changing environment)- those three
elements are the essentials for maintaining and perpetuating life. Those
elements evolved due to the self-referential, self-organizational nature of
life, emerging from the Cosmic Singularity/Big Bang, the recoil caused by
Newton's Third Law of Motion- every action having an equal and opposite
reaction- giving rise to both physical (Black Holes, Stellar Evolution) and
chemical (balanced chemical equations) phenomena, as well as to life
itself, beginning with the unicell. As a reality check, all of this relates
to Hughlings Jackson, the 19th Century Neurologist's observation that
dissolution of brain structures due to various brain diseases are
characterized by the reversal of the order in which various brain
structures appeared during development/phylogeny.

On Sat, Feb 24, 2018 at 8:21 AM, Henriques, Gregg - henriqgx <
[log in to unmask]> wrote:

> John,
>
>   Thanks very much for this summary of your work. As you note, I have been
> fascinated to learn about your perspective since November. I was wondering
> if you could share some how you see your work in relationship to the modern
> evolutionary synthesis, the idea that biological complexity evolves as a
> function of natural selection operating on genetic combinations through
> time.
>
>
>
> Over the course of my study, I have came to see that biology consists of
> three big ideas: 1) natural selection; 2) genetics, and 3) cell
> bio-physiology. And one of the reasons I have been drawn to your work is
> that, prior to meeting you, I too had (a more intuitive) sense that cell
> physiology was not really woven into the picture. Your work clearly does
> this. However, I still am sometimes a little unclear on where your ideas of
> first principles of physiology and related concepts stands in relation to
> the modern synthesis. Can you say a bit about that?
>
>
> Best,
> Gregg
>
>
>
> *From:* tree of knowledge system discussion [mailto:TOK-SOCIETY-L@
> listserv.jmu.edu] *On Behalf Of *JOHN TORDAY
> *Sent:* Thursday, February 22, 2018 2:41 PM
> *To:* [log in to unmask]
> *Subject:* Dear ToKers
>
>
>
> Dear ToKers,
>
> Gregg has asked me to introduce myself in anticipation of my contribution
> to the April meeting. I am a Professor of Pediatrics, Ob-Gyn and
> Evolutionary Medicine at UCLA. I have a PhD in Experimental Medicine from
> McGill University, my first Faculty position was at Harvard Medical School,
> then at U Maryland, and now at UCLA.
>
>
>
> I began an email correspondence with Gregg several months ago, finding
> common ground between us in our mutual desire to bring new order to both
> psychology and biology/medicine. My current perspective emerged via the
> realization that I could exploit the cell biology of embryonic development
> and phylogeny (my research career) to trace the evolution of the mammalian
> lung back to its unicellular origins. But when I turned to the evolution
> literature on developmental biology, or EvoDevo, there was literally *no
> cell biology*, initially due to a historic glitch caused by the absence
> of cell science to propel evolutionary biology in the 19th century; so
> instead the evolutionists embraced genetics, and never let go. But cell
> biology underpins all of contemporary biology and medicine. I have made
> efforts since that realization to introduce my cell biologic perspective on
> evolutionary biology to the evolution of physiologic traits such as the
> lung, kidney, skin and bone.
>
>
>
> There are certain key concepts that have helped me to recapitulate
> physiologic evolution from the unicellular state forward, primarily the
> principle of cell-cell communication mediated by growth factors and their
> receptors as the mechanism for embryologic structure and function, to which
> I have contributed beginning in the early 1970s. That, in combination with
> the observation that evolution is a series of pre-adaptations or
> exaptations or co-options, offering the opportunity to see the
> interrelationships between different physiologic adaptations based on
> cell-cell communication mechanisms. But above all, the theory that the
> cellular internalization of external factors in the environment such as
> ions, gases, heavy metals, bacteria, gravitational forces,
> compartmentalizing them and making them useful as physiologic traits is key
> to understanding the origins of life, not as the Anthropic Principle that
> sees us *in this environment*, but rather the realization that *we are
> ‘of’ this environment. The **“*Endosymbiotic Theory*”* can be understood
> based on the unicellular origins of life and the subsequent cell-cell
> communication mechanisms that fostered complicated physiology of
> multicellular organisms.
>
>
>
> I mention all of this because I am of the opinion that all of the organs
> of the body, including the brain/perceptual consciousness evolved in tandem
> with the visceral organs. For example, there was a big breakthrough in
> understanding the evolution of the brain back in 2003 (Holland ND. Early
> central nervous system evolution: an era of skin brains? Nat Rev Neurosci.
> 2003 Aug;4(8):617-27) when Holland showed that there was a continuum from
> the central nervous system of worms to vertebrates based on its
> phylogenetic origins in the skin, or the skin-brain hypothesis. The skin is
> a highly underappreciated organ, which was hypothesized to be the origin of
> all complicated physiology in vertebrates (Torday and Rehan. Evolution, the
> Logic of Biology. Wiley-Blackwell, 2017).
>
>
>
> It is here that I share interests with the folks on this lis. I know Gregg
> has become quite interested in the view of the human as an extended cell
> and the braiin as the skin, folded inward. I have been able to exploit the
> idea that the first cell evolved from the immersion of lipids in water,
> both components coming from the frozen asteroids that pelted the early
> Earth before there was an atmosphere that could oxidize them. But that
> raises the question as to what was the basis for the spontaneous formation
> of lipid-based protocells? Traditionally, that has been attributed to the
> self-referential, self-organizational properties of life, giving rise to
> the First Principles of Physiology (FPP), which were generated by the
> protocell defined by its lipid membrane, distinguishing the internal and
> external ‘environments’. The FPP are constituted by negative entropy, or
> negative Free Energy within the cell, chemiosmosis, the most primitive way
> of generating bioenergy, intracellular membranes partitioning negative and
> positive ions on either side of them to generate an electrical current  to
> sustain negentropy, and homeostasis as the monitoring mechanism for the
> interrelationship between the entropy within and outside of the cell.
>
>
>
> I have hypothesized that the origin of self-referential self-organization
> was the Singularity of the Big Bang, given that for every action there is
> an equal and opposite reaction (Newton’s Third Law of Motion). With that
> cellular molecular mechanistic linkage from contemporary physiology,
> referring all the way back to its origins in the Singularity/Big Bang, I
> have speculated that that is the origin and continuum of Consciousness
> itself, or the Hard Problem (David Chalmers), how we ‘know that we know’.
> Hameroff and Penrose have speculated that the brain integrates information
> through the microtubules of the cytoskeleton of neurons. Yet all cells have
> cytoskeletons, so it is feasible that there is integration of the somatic
> and CNS microtubules, which Head and Holmes [1911], and more recently
> Haggard and Wolpert referred to as "Disorders of Body Scheme?"
>
> The other breakthrough idea that may form common ground between physiology
> and psychology is the concept of the ‘Phenotype as Agent’ (Phenotype as
> Agent for Epigenetic Inheritance.
> <https://urldefense.proofpoint.com/v2/url?u=https-3A__www.ncbi.nlm.nih.gov_pubmed_27399791&d=DwMFaQ&c=eLbWYnpnzycBCgmb7vCI4uqNEB9RSjOdn_5nBEmmeq0&r=HPo1IXYDhKClogP-UOpybo6Cfxxz-jIYBgjO2gOz4-A&m=9b6-Whll2uErOHRlZZa8ChznUHOERyKe4VKjG2ay8IM&s=0WNA0rZjxBg3g7BZYjz7NwLopdPMNFoaiEOI3van09U&e=>
> Torday JS, Miller WB. Biology (Basel). 2016 Jul 8;5(3)). That notion
> emerged from the hypothesis that the unicell was the first Niche
> Construction (NC), NC being the concept that organisms generate their own
> immediate environments. So by combining endosymbiosis with NC,
> hypothesizing that the unicell internalized its environment (The Cell as
> the First Niche Construction.
> <https://urldefense.proofpoint.com/v2/url?u=https-3A__www.ncbi.nlm.nih.gov_pubmed_27136594&d=DwMFaQ&c=eLbWYnpnzycBCgmb7vCI4uqNEB9RSjOdn_5nBEmmeq0&r=HPo1IXYDhKClogP-UOpybo6Cfxxz-jIYBgjO2gOz4-A&m=9b6-Whll2uErOHRlZZa8ChznUHOERyKe4VKjG2ay8IM&s=NyrSjKZhogyEQf8D8Kz05MmildVpKMLOmoRbTJ8GJdc&e=>
> Torday JS. Biology (Basel). 2016 Apr 28;5(2)) as described above, that
> the process of evolution can be seen as a continuum from its origins to
> present day physiology, consciousness being the manifestation of that
> process at the level of being aware of one’s surroundings, both internal
> and external.
>
> Just to be more concrete, as mentioned, the cytoskeleton may act as the
> structure within the cell that acts to communicate between cells throughout
> the body. Penrose has shown that anesthetics bind to the catalytic site
> within tubulin, inhibiting its formation, linking the cytoskeleton to
> consciousness. And when yeast, primitive unicellular relatives of
> vertebrates, are put in zero gravity they lose their abilities to polarize
> (unaware of up/down/left/right) and cannot reproduce due to collapse of
> their cytoskeleton. So depriving this organism of its sense of gravity
> renders it dissociated from its ‘consciousness’ of its surroundings, i.e.
> it is unconscious. Thus the putative link between the cytoskeleton,
> consciousness and Cosmic Consciousness.
>
> This way of thinking about the continuum from physiology to our immediate
> perceptual consciousness of being, to the Consciousness of the Cosmos,
> conventionally referred to as something greater than ourselves, as the
> product of the iterative internalization of the environment, or the
> endosymbiosis referred to above, offers an opportunity to understand
> these processes mechanistically. And as I have proposed to Gregg, the
> ‘joints’ in his ToK can be understood as part and parcel of the same
> continuum mechanistically, merging his scheme with mine. For example, I
> have previously used the cell-molecular approach to ‘predict’ the evolution
> of endothermy (A central theory of biology.
> <https://urldefense.proofpoint.com/v2/url?u=https-3A__www.ncbi.nlm.nih.gov_pubmed_25911556&d=DwMFaQ&c=eLbWYnpnzycBCgmb7vCI4uqNEB9RSjOdn_5nBEmmeq0&r=HPo1IXYDhKClogP-UOpybo6Cfxxz-jIYBgjO2gOz4-A&m=9b6-Whll2uErOHRlZZa8ChznUHOERyKe4VKjG2ay8IM&s=H-CqJb-JiKg0wEsfV0Zyab7VRT69LWebGj5yeqZJB8I&e=>
> Torday JS. Med Hypotheses. 2015 Jul;85(1):49-57), largely based on the
> opposite effects of physiologic stress on ‘fight or flight’ versus
> meditation/hibernation. Such ideas may help to further elucidate the nature
> of consciousness, and the continual line from the Bigh Bang, through the
> FPP of the unicell, all the way to this email exchange.....Please don't
> hesitate to comment/critique......Best, John Torday
>
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