Modern biology remains descriptive, post-dictive, non-mechanistic and
non-predictive. It only appears to be effective because it is associated
with the actual mechanisms involved. Look at the story of ulcer, which was
thought to be due to stress for centuries. Turns out its caused by H
Pilori, a gut bacterium, and sure the infection can be brought on by
stress, but that's not the primary cause. And all the money spent on cancer
research and treatment for a disease we don't know the cause of. By
analogy, biology is where chemistry and physics were as alchemy and
astrology. So for example, the human genome was predicted to be at least
100,000 genes.....last I looked we are down to 19,000 and counting. Biology
and medicine remain associations and correlations, whereas the way that I
have reduced evolution to cell-cell communication, ascribing to the First
Principles of Physiology, diseases can now be seen as cellular
maladaptations, not gene mutations. Only ~3% of human genetic diseases are
Mendelian (1 gene,=1 disease); the other 97% are probably epigenetic. Other
than trauma and infectious disease, *medicine based on biology is not
predictive*. Why do you think that the breakthroughs in medicine have been
counterintuitive and serendipitous, almost without exception? The only
discipline in medicine that is rational is infectious disease because we
know what causes it, so we can use Koch's Postulates to diagnose and treat
it. You know the old saw about the guy who is given a clean bill of health
by his Cardiologist, and walks out of the office and drops dead of a
massive coronary.

I created a clinical laboratory at Brigham and Women's Hospital, the
teaching hospital for Harvard Medical School in 1976. It was dedicated to
predicting whether newborns had mature lungs or not, the rate-limiting
factor for survival at birth. I devised a sensitive and accurate
biochemical test that was 97% predictive because we knew that Respiratory
Distress Syndrome, the disease the Kennedy baby died of in 1962, was due to
lung surfactant deficiency. The test was published as the lead article in
the New England Journal of Medicine in September, 1976. When I left Harvard
in 1991 the lab was performing 5,000 tests for lung development annually,
whereas conventional labs do about 200 tests. Fast forward to 2008. I get a
phone call from one of my former lab technicians who is now the Pathologist
in charge of all of the biochemical testing at Brigham and Women's Hospital
(it's a long story). He tells me that he is being forced to change the lung
maturity testing from the biochemical assay I developed in 1976 to a
faster, cheaper, but highly inaccurate method I am quite familiar with (so
the hospital could make more money because the assay is not as labor
intensive). In telling me this, he says that the only tests in the entire
suite of tests run in his labs are my assay and the assays for heart
enzymes that indicate whether and how intense an heart attack was. All of
the other tests are confirmatory, not predictive. This is the state of the
art in 'evidence-based' medicine. I maintain that if medicine were not
essential for society we wouldn't be expending such huge amounts of money
on such a non-scientific discipline.

As I have said before, the difference between Darwinian and Epigenetic
evolution is like the difference between Newtonian and Einsteinian Gravity
Theory, the former being descriptive, the latter mechanistic. So Newtonian
physics describes how bodies attract one another, but does not fit with
Relativity Theory. Einsteinian Gravity Theory, on the other hand, is
consistent with Relativity Theory, explaining that gravity is the result of
deformation of the fabric of space-time. allowing for a cohesive way of
thinking about physics rather than anecdotes. Based on Occam's Razor, or
parsimony, the Einsteinian perspective is correct because it is the
simplest, most parsimonious way understanding the two ways of explaining
the same phenomenon. The same would be the case for Darwinian vs Epigenetic
evolution as I have described it. Genes are not what sense changes in the
environment that signal for evolutionary change, cells are. You may argue
that what I have described is the same as Darwinian evolution in that even
'internal selection' will ultimately comply with survival of the fittest,
but its not about the adults selecting one another for reproduction, and
the number of offspring being the measure of evolutionary success,  which
are proxies for what actually occurs during evolution. it's the quality of
the fit with the environment as determined by the phenotype interacting
with the environment to collect epigenetic marks that is the mechanism that
underlies adaptation. So it's really 'apples and oranges' when it comes to
Darwinian v Epigenetic evolution.

On Sat, Feb 24, 2018 at 12:22 PM, Henriques, Gregg - henriqgx <
[log in to unmask]> wrote:

> So what, exactly, are you saying about the modern evolutionary synthesis?
> Are you saying it is incomplete or are you saying it is completely wrong?
>
>
>
> I just finished the book, *The Gene: An Intimate History*. A great book,
> IMO, that describes the enormous developments in biology over the past 150
> years or so. The fundamental point of the book is that the merger of
> Darwin’s theory of natural selection with the science of genetics led to
> huge advances in our understanding. That seems to be a justifiable
> statement to me.
>
>
>
> Are you saying that this is all a mirage? That the whole foundation of
> modern biology is *completely* misguided? If so, this feels hard for me
> to believe. It seems much more palatable to say that it is incomplete. How
> can we possibly explain all the progress that has been made? Granted the
> picture might change quite fundamentally as we pull in cell bio-physiology
> and other insights (e.g., perhaps analogous to how quantum mechanics and
> general relativity changed our understanding of physics). But you seem
> dismissive here of cornerstones of biological knowledge. Can you help me
> sort that out?
>
>
> Best,
> G
>
>
>
>
>
>
>
>
>
> *From:* tree of knowledge system discussion [mailto:TOK-SOCIETY-L@
> listserv.jmu.edu] *On Behalf Of *JOHN TORDAY
> *Sent:* Saturday, February 24, 2018 12:10 PM
> *To:* [log in to unmask]
> *Subject:* Re: Dear ToKers
>
>
>
> 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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