In God We Rust: the Beauty of Unintelligent Design



In God We Rust: the Beauty of Unintelligent Design

From Cells to Societies: A Dynamic Fractal

Dr. Robert Melamede, Ph.D.  drbobmelamede@me.com 

Edited by Dr. Mathew Hogg, Ph.D.

Phoenix Tears Foundation, Denver CO, USA; CannaHealth Labs, Colorado Springs CO; Second Chance, Ecuador; CannaSapiens, Belgrade Serbia; Nostic Cannabis Cluster,  Kingston Jamaica

Abstract: What if the standard random mutation-based view of the evolution of species and cancers is incomplete, and instead of being an all-encompassing framework it actually misses a much bigger picture, namely, the fundamental creative nature of Nature? What if the reality of ongoing creation (GOD, General Open-System Dynamics) has been replaced with a stagnant dogma of accident-driven evolution? If we reverse our current perspective, previously miraculous, improbable events may be scientifically understood from first principles that emerge by embracing a far from equilibrium thermodynamic perspective based on the work of Nobel laureate Ilya Prigogine.

 



Introduction: Man's understandings naturally start from the simple and move over time to the more complex. But what is simple, what is complex, what is time, how and why is there change? An integration of physics and biology emerges after considering these concepts from the perspective of far from equilibrium thermodynamics as developed by Nobel laureate Ilya Prigogine. Prigogine’s work provides an alternative foundation for understanding physics and life. In his last book, The End of Certainty1, he fully embraces his earlier work (From Being to Becoming2) and concludes that flowing energy has a creative organizing capacity that is fully consistent with the Second Law of Thermodynamics, as extended by Prigogine for open systems. His perspective can be readily extended to living systems, creating the “Physics of Life” 3, the physical basis for a systems biology perspective.



It is a well-established paradigm that the genetic transfer of information occurs through the transcription of DNA to RNA followed by the translation of RNA into proteins, which then integrate into life’s concert of homeostatically regulated enzymatic activities. A broadly accepted hypothesis in the scientific community is that life and evolution are the result of an accumulation of improbable accidental events that have “miraculously” been retained by evolution. This line of thinking is a natural consequence of classic foundational physics based on a logical mathematical formalism of timeless equilibrium. A logical extension of this perspective leads to the conclusion that time is reversible. However, the appearance of irreversibility occurs in a time-biased fashion, there is a direction to times. Thus there is a discrepancy between these conclusions and the everyday experiences of living organisms. We are guided by of the arrow of time from birth till death. Random statistics cannot explain life; it is too improbable to exist from a timeless perspective. 



Prigogine’s work explains how flowing energy can naturally organize matter to create flow-dependent structures that are thermodynamically stabilized by sufficient entropy production. Evolving complexity from this seminal thought provides a physical foundation for the emergence of life and evolution, driven by the creative force of nature. Creativity, which can be thought of as solutions of systemic complexity that degrade potential, emerges when far from equilibrium systems are pushed to a flow-dependent critical point, at which time the system might spontaneously undergo a far from equilibrium phase space change to a higher level of spatial and temporal organization (negative entropy), or it might collapse to a lower level of organization that might be flow dependent or not.

What is a fractal and what is a dynamic fractal? A system (a collection of molecules) is timeless when at equilibrium because entropy (disorder) is at a maximum and free energy (the ability to do anything) is at a minimum. Hence, everything is fully random and devoid of useful information (negative entropy). There is no change and thus no way to manifest time. In contrast, a network of localized inorganic, flow-dependent reactions interacting, feeding, and being fed by each other can ultimately lead to the far from equilibrium phase change known as life.

Environmental conditions, from the sub-cellular to the planetary, create flow-dependent structures that are in turn affected by their own creation, thus creating what is known as a dynamic fractal. Consequently, a complex landscape of evolving selective pressures maintains ongoing homeostatic ability with constant dynamic adaptability. Evolution of all complex systems, across all scales of time and space, are driven by the flow of excess energy potential. The flow of living systems is maintained by appropriate cellular damage prevention (antioxidants) and recycling (autophagy) that are in constant play to overcome the friction of life, namely excess free radical-promoting entropy. Life and evolution must occur because they are driven by the flow of energy. Such biological conclusions that emerge from the new theories of far from equilibrium thermodynamics shake the foundations of our universally accepted truths while providing direction for the future.

It appears that the scientific establishment has failed to grasp the genetic consequences of life’s most fundamental property, adaptability. Currently, the physical foundations of life are ironically embedded in a dead, equilibrium-based perspective of random statistics. However, the ability of flowing electrons to create what are essentially statistically impossible molecular distributions, such as those seen in the Belousov–Zhabotinsky reaction 4, suggests a clear parallel with the metabolic redox processes of living systems. They can account for the emergence and evolution of life, as well as all manifestations of human consciousness and all of our societal structures (financial, political, religious, etc.), thus a more advanced perspective of humanity’s place in the chemistry set of evolution needs to be developed and implemented for natural harmony.

In order for flowing energy to maintain the high level of adaptability characteristic of living systems, for now best exemplified by human beings, there is a need for sophisticated feedback mechanisms that can monitor the balance between negative entropy accumulation and entropy production. The entropy exported by a flow-dependent system must be greater than the negative entropy retained in order for the system to remain stable. Is there a common characteristic that can be monitored to maintain homeostasis? If so, what is its nature, and what are the biological manifestations by which homeostatic adaptability is accomplished?

The answer to these questions will integrate free radical-induced biochemical changes (homeostatic and/or damaging) with the intrinsic truth that in a human population everything is regulated by endocannabinoid activity 5 from conception to death. By definition, half the population will be above and half will be below average for any particular phenotype, for example, forgetfulness. How might forgetfulness be involved with evolutionary adaptability? Clearly, from the perspective of adaptation, there should be an advantage when incorrect information is replaced with updated new, and presumably more correct, information. The nature of all flow-dependent structures will always reflect the sources that created and feed them. Consequently, the harmony of exchanges between these structures with their environment must constantly adapt as the environment adapts to nature’s ever unfolding creativity. The consequences in a population that result from a distribution of cannabinoids’ effects on memory will be reflected in the flow-dependent structures that constitute ourselves and those that we create as complexity increases and actually creates time (from cells to society).

Memory is intrinsically a fundamental asset to living systems because it allows for responsive non-random behavior. As the complexity of organisms increases, the consequences of memory permeate the organism’s hierarchy. Superficially, it might seem that a greater memory capacity would naturally be beneficial. However, with the complexities of human consciousness, forgetting has become essential for optimizing adaptability. People with lower levels of cannabinoid activity, both endogenous and consumed, will typically experience greater levels of stress because of their inability to forget stresses from the past. This phenotype becomes a positive feedback loop because at the same time these individuals often suffer from the inability to deal with current stress due to lower endocannabinoid activities. Consequently, epigenetic changes institutionalize behavior. As will be explained below, metabolism to epigenetics to genetics is the main theme presented.

People with above-average levels of cannabinoid activity, for any phenotype under consideration, will have different characteristics than those with lower levels. Without sufficient cannabinoid activity, a person will typically spend more of their conscious time looking backwards because the past represents a known, even if this known is unpleasant. It is safe because nothing is new and no adaptation is required. Such individuals can be referred to as Backward-Looking People (BLPs). The more stressed such individuals become, the greater their tendency to try to control the future based on dominant forgotten and unforgotten stresses of the past. In contrast, Forward-Looking People (FLPs) have a greater tendency to embrace the unknown because they are more optimistic and more readily forget the stresses of the past. The optimistic FLP may be predisposed to taking more chances than the pessimistic BLP. Individuals with the FLP phenotype are more likely to experiment with the unknown and maybe even dare to try cannabis. This simple notion invalidates so many epidemiological studies that assume a random distribution for whatever characteristic is being examined. For example, such studies assume that there is an equal probability of cannabis use among sick versus healthy individuals, between those suffering pain and those not suffering pain – how foolish!

Because it is at the heart of so much behavior, it is important that we have a realistic definition of “stress”. Stress is any change to which a flow-dependent homeostatic system must adapt, for good or for bad, for systemic survival. Homeostasis always requires continuous adjustments of flow. As within each individual, in a dynamic fractal-like manner, the collective consciousness of a population is intrinsically regulated by the balance between BLP and FLP activities. Relaxation is a multidimensional biological process facilitated by cannabinoids because of their ubiquitous homeostatic ability to regulate free radical activity. Cannabinoids are adaptogens 6, and without sufficient cannabinoid activity a person is naturally more fearful of the unknowns that are intrinsic in the future 7. Such people are driven to control the future by staying in the past. Their conservative nature emerges and thus provides both a biological and philosophical rationale for forming political and religious aggregates of like-minded thinkers in an attempt to achieve social stability.

However, social stability must be balanced with progress because everything is always changing. The question, then, is how to best optimize for a successful future? 8 A natural starting point would be to understand the nature of our creation so that we can become more harmonious and synergistic with it, and understanding the physics and biological manifestations of flowing energy seems to be logically mandated. With sufficient flow and evolving complexity, nonlinear rearrangements will occur as they always have in the past. From the perspective of the evolving human mind, what might we expect from such a system? The physical foundations of evolving biological systems will echo throughout a dynamic system’s evolving complexity. Social systems 9, including education, politics, finances, and international interactions will spontaneously reorganize as the human brain evolves concurrently, as it always has, with increasing cannabinoid activity. Canna sapiens will emerge from Homo sapiens as a higher and less destructive nature normalizes.

How might the integration of far from equilibrium thermodynamic thinking affect our understanding of life and evolution? As mentioned above, it is a well-established paradigm that the genetic transfer of information occurs from DNA to RNA to proteins, which are integrated into life’s concert of homeostatically regulated enzymatic activities. A broadly accepted hypothesis in the scientific community is that life is the result of an accumulation of improbable accidental events miraculously retained by evolution. This line of thinking is a natural consequence of foundational physics based on a logical mathematical formalism of timeless equilibrium (maximum entropy, minimum free energy). The logical extension of such thinking leads to the conclusion that time is reversible. Thus the appearance of irreversibility in our everyday world 8 that occurs in a time-biased fashion does not fit with the established paradigm, and thus there is a fundamental discrepancy between a classical understanding of Newtonian physics and the everyday experiences of living organisms that are guided by of the arrow of time. Random and time-independent statistics cannot explain life because life is too improbable to exist.

Before new biological concepts can be developed and examined, the physical underpinnings of life must be re-considered. Prigogine’s work as described earlier provides a novel foundation that can be developed into a synergistic understanding of both physics and life. Surprisingly, it appears that the scientific establishment has failed to grasp the genetic consequences of life’s most fundamental property, adaptability. Currently, the physical foundations of life are ironically embedded in a dead, equilibrium perspective of random statistics. The ability of flowing electrons to create a statistically impossible molecular distribution, such as that seen in the Belousov–Zhabotinsky reaction 4, provides a clear parallel with the metabolic redox processes of living systems.

Life and evolution are driven by the inherent creative force of nature. Creativity, which can be considered as solutions of systemic complexity that degrade potential, emerges when far from equilibrium systems are pushed to a flow-dependent critical point at which the system spontaneously undergoes a far from equilibrium phase change to a higher level of spatiotemporal organization (resulting in negative entropy). Conceptually, a network of localized, inorganic flow-dependent reactions interacting, feeding, and being fed by each other can ultimately move a system a sufficient distance from equilibrium until the far from equilibrium phase change of life occurs and is repeated throughout the evolution of species.

Environmental conditions, from the sub-cellular to the planetary, create flow-dependent structures that are in turn affected by the systemic interactions resulting from their own creation (in other words, they form a dynamic fractal). Consequently, a complex landscape of evolving, selective pressures maintains ongoing homeostatic ability with constant dynamic adaptability. The evolution of all systems, across all scales of time and space, is driven by excess energy potential, and this is maintained at the cellular level by appropriate prevention (antioxidant) and recycling (autophagy) efforts that are in constant engagement to overcome the consequences of the friction of life, free radicals. Life and evolution must occur, as dictated by the flow of energy, but they are shaped by free radicals. Thus the next part of this manuscript presents a metabolic perspective on the evolution of species and cancers.

Life’s main energy sources, carbohydrates and lipids, are not functionally equivalent 10,11. Carbohydrates preferentially feed the efficient, but dangerous, electron transport system that promotes and supports differentiated cellular functions such as nerve transmission, muscle contraction, and hormone production. Essentially, efficient energy production promoted by metabolizing carbohydrates through the electron transport system is the functional equivalent of a nuclear reactor that sometimes leaks radioactivity. The electron transport system in the mitochondria provides efficient, clean energy in the form of ATP. However, mitochondrial energy-producing metabolism, like the nuclear reactor that leaks radioactivity, produces free radicals under conditions of inappropriate mitochondrial input 12 or restricted outflow. When excess free radicals are produced, cells will usually begin to synthesize lipids through well-established pathways from the whole body to the subcellular in order to reduce excess free radical production that would otherwise result from excess carbohydrate catabolism. From an entropic perspective, both intracellular and social recycling enhance negentropic activity, and the dialogue between these systems at different levels allows a state of health to emerge from living systems and their societies (mathematically speaking an attractor).

In vertebrates, cannabinoid receptor 1 (CB1)/electron transport-driven ATP production, and subsequent production of all other cellular components, is balanced by CB2-driven recycling of free radical-damaged cellular components. Additionally, because fat burning is promoted by CB2 activity 13, this might also promote beta-oxidation–dependent symmetrical stem cell expansion as occurs in embryonic stem cells 14. In contrast, CB1 activity promotes electron transport system-driven stem cell differentiation. The plasticity of energy flow in vertebrate systems is emphasized by the presence of CB1 in the mitochondrial membrane 15 and the components of the electron transport system within the plasma membrane of human cells 16. In essence, what we as a species are exploring is the possibility that the source of human regenerative capacity is implemented through the endocannabinoid system. We are just beginning our journey out of ignorance.

The underlying concept is that survival of the fittest means survival of the most adaptable, not the strongest, fastest, or smartest. Consequently, the initial selection for a systemic state occurs at the metabolic, not the genetic level. Metabolic imbalances promote excess free radical production that leads to focused epigenetic modifications, followed by focused changes of the genes and their controlling regions that are responsible for survival. DNA damage and its repair provide a source of the changes that characterize evolution 17, including gene duplications, recombinational events, sloppy DNA polymerases that bypass damages, retroviral activation, etc. Consequently it seems likely that evolution, for the most part, occurs by metabolically selecting/directing needed, nonrandom, free radical-promoted genetic change by selecting metabolic states in a multi-gene fashion that promote the systemic metabolic survival state. Metabolically directed evolution is, therefore, quasi-Lamarckian in that it argues that adaptation to the environment by an organism can be passed on to the organism’s progeny.

Statistically, the above perspective makes intrinsic sense. DNA is a complex molecule that is unlikely to randomly form from its components. How is it, then, that DNA, an estimated 50,000,000,000 tons of which exists on the planet Earth 18, has become, probably, the most successful molecule in the universe? The answer can be found in the success of molecular cooperation driven by flowing energy and entropy production. Flowing energy driving evolutionary change provides an easy to understand explanation for the evolution of life and species, and similarly provides an explanation for cancer drug resistance and the genetic diversity of tumors. Potentially important beneficial health consequences, especially with respect to cancer, need to be considered. The existing scientific/medical framework has been unsuccessful in creating the desired health outcomes, but a simple shift in perspective creates an entirely new reality when considering the causes and treatments of cancers.

The far from equilibrium approach to understanding life intrinsically leads to the all-pervasive role of flowing energy in creating and sustaining life. Numerous reports coming from varying biological specialties are increasingly finding metabolic solutions for health concerns. The following is an extreme example that demonstrates the utility of a cannabis-driven metabolic approach to treating cancers that result from genetic defects in the cell’s ability to repair ultraviolet light-induced mutagenic DNA damages. The patient below suffers from xeroderma pigmentosum 19, and intensive cannabis therapy has resulted in the reversal of many of the phenotypic symptoms of the disease, including the elimination of pain, ending depression, healing melanoma, healing tongue and lip cancers, and restoring sight by reducing inflammation around the eyes (personal communication, B. Radisic).

Is there a connection between the lack of nucleotide excision repair seen in xeroderma pigmentosum and the potential for cannabinoids to regulate free radical production and associated base excision repair? It is important to remember that when we are dealing with open systems, we are focusing on dynamic, not static, processes. Consequently, small perturbations can be amplified into macroscopic systemic changes (the well-known butterfly effect). The human body has approximately 15 trillion cells that every day suffer from at least 30,000 oxidative base damages where one damage, at one point in time, and in the wrong gene could kill a person if it amplifies through the system to create a lethal cancer. Common sense dictates that an extensive amount of life's organization must be devoted to protecting life from excess free radical damage and the organizational disruption that free radicals impose on cellular biochemical harmony. When flow-dependent organization decreases to a thermodynamic critical point, it leads to systemic collapse, commonly known as apoptosis.

One of the most dramatic examples of metabolic adaptability in response to potential free radical damage is seen during S-phase of the cell cycle. The electron transport system efficiently provides the needed energy to build up a cell’s negentropic flow during the G1-phase of the cell cycle. The resulting free radical production and subsequent damage to all cell constituents form part of the homeostatic feedback loop that directs cells to shut off the excess free radical production coming from the electron transport system and to turn on the safe, but inefficient, process of aerobic glycolysis, a.k.a. the Warburg effect 20.  

What might the consequence of this altered metabolism be? Imagine a population of cancer cells all having a single mutation in the same gene. An unsynchronized population will have individual cells in all phases of the cell cycle. Those cells that cannot efficiently amplify free radical imbalances to cause apoptosis will survive any assault designed to kill by this cell death mechanism. Consequently, cells in S-phase will have a greater probability of surviving because free radical-induced damages and their repair will be focused on replicating and transcribed genes. The abnormally prolonged transcription of metabolic patterns will naturally lead to mutagenesis that promotes successful metabolic patterns. Thus, many cancers powered by aerobic glycolysis were probably initially metabolically selected for prior to becoming imbedded in genetics.

Similarly, glutaminolysis, driven by the MYC oncogene 21, provides an additional ATP source that maintains the carbohydrate-driven differentiated state by supporting the production of Krebs cycle intermediates. In contrast, as with aerobic glycolysis 22, glutaminolysis 23 and AMPK activity seem to be mutually exclusive, again separating synthetic and differentiated pathways from those responsible for recycling of cellular components damaged by free radicals. An overview of metabolic options explains both the origins and treatment possibilities of cancers, as well as all other diseases. The use of chemotherapy and radiation 24 simply selects for the surviving metabolic states that subsequently become institutionalized as genetics. In contrast to the killing induced by chemotherapy and radiation, autophagy moves the cell to a lower level of communication with its environment while decreasing its internal entropy through recycling of the damaged components that were the indicators of the need to recycle in the first place. Thus autophagy can become a cell’s ultimate survival mechanism 25, which is good when the cell survives and rejoins the community of cells as a harmonious part of the greater structure. DNA is the record of metabolic success.

Adaptation requires that first a unique biochemical state is selected that is typically maintained by epigenetics after the initial metabolic adaptation resulting from countless post-translational modifications. Consequently, excess free radical damages, due to maintaining and expanding the original metabolic imbalance, are focused on the transcriptionally active genes 26 that promote survival. The damages themselves, the DNA nicks, and the single-stranded regions that are undergoing repair can promote recombinational events, gene duplications, and mutations, providing new material for evolution. For example, stalled DNA and RNA polymerase molecules can generate a variety of novel DNA outcomes 27 28 29. The significance of DNA architecture is emphasized by the fact there exists both global DNA repair as well as transcription-coupled repair 30 31.

The above proposal clearly challenges conventional modern interpretations of molecular genetics and its role in evolutionary change. The evolution of species and cancers is for the most part not the result of randomly created mutations on a genome wide level, but instead focuses on mutational change where it is needed, in the genes that are responsible for survival in any particular metabolic state. Add to that the intellectual perturbation of corroborated, unpublished studies (personal communication YW Kow, Z Hatahet) that demonstrated that fat burning, drug/radiation-resistant HL60 monocytic cells do not express base excision repair enzymes. In contrast, these repair enzymes are expressed in the drug/radiation-sensitive parent cell line (Melamede and Stubbs, unpublished results).

In conclusion, life is a natural endpoint after a billion years of energy-driven chemical complexity evolving in the test tube called planet Earth. We now have a sufficient scientific foundation to understand the nature of that process so that human health and planetary health may be best addressed for healthy survival. Each individual living organism is simply a flow dependent, quantized probe in adaptability that is adapting as the complexity of the chemical reaction moves into the future.  Embracing adaptability facilitates movement into the future. Too often, unfortunately, cannabinoid-deficient BLPs currently run the world, driven by greed and power, a natural consequence of a more primitive state. In contrast, the activist medical cannabis community that is leading the Cannabis Awakening is successfully using cannabis-based metabolic approaches (whether they know it or not) to control cancers, HIV and associated illnesses, dementia, dyslipidemia, Kaposi sarcoma, autoimmune diseases, pain, fibrotic illnesses, and numerous other age-related inflammatory diseases based on imbalances in body systems.

The concepts are simple. A state of health can only be achieved with a balance between damage production and repair and prevention. For the first time we have a simple definition of health, which can be measured by moving the system farther from equilibrium in a sustainable fashion. The complexity of an organism grows as it matures both by increasing its amount of matter as well as by increasing its organization (negative entropy). Aging and age-related illnesses promote a return to equilibrium, and death is just a far from equilibrium phase change to a lower level of organization. It is encouraged to our ignorance. Once a human reaches adulthood they no longer move farther from equilibrium by growing in size unless, for most people, they are just getting fatter. A fat body is farther from equilibrium. If burned, the fat would release more energy than a thinner body of equal weight. In terms of health-promoting complexity, a fat, unfit human is closer to equilibrium. Body fat is simply an indication that the organism was consuming too many carbohydrates. In order to not burn them and generate excess free radicals, the cells turn carbohydrates into fat. The popular ketogenic and paleo diets promote cellular recycling, consistent with the increasing appreciation the metabolic underpinnings of so many disease conditions.

The entire planet is now undergoing a far from equilibrium phase change characterized by fluctuations of the intensive variables of the system that approach infinity. From a physicochemical perspective, these are measureables that occur prior to a far from equilibrium phase change. Today we see supporting indications for this possibility on the global level in the form of fluctuating weather patterns, novel migrations of species (including humans), inappropriate distributions of chemicals such as the plastic poisoning the oceans and the nanoparticles that we eat and breathe, etc. The energy and associated information flow in the modern world is generating excess stress, and hence increasing our free radical load. Our ignorance regarding the physics of life keep us supporting wealthcare instead healthcare.

Today “citizen scientists” all around the world are dramatically improving their health with a variety of cannabis-based preparations that contain highly variable biologically active landscapes. Typically people are treating themselves at home, often in the absence of medical oversight. Metabolically, every human is different, even twins. In order to most effectively use cannabis, each patient needs to develop a relationship with cannabis so they can match their needs with what different strains have to offer. As the godfather of cannabis, Dr. Mechoulam has stated, "Cannabis is a treasure trove of pharmacologically active chemicals.” Globally, cannabis activists are educating people who are successfully treating themselves for illnesses and conditions for which the healthcare system has failed to provide any satisfying real health-promoting solutions.  Autism promoted by vaccines, cancers, metabolic syndrome, and autoimmune diseases are all promoted by a toxic environment, toxic food, and bad information promoted by healthcare and by society in general. These people are recognizing fake medicine and fake science, and they are demanding cannabis freedom for survival.

More and more people are recognizing the harm that ignorant, corrupt governments, in collusion with the biomedical industry, are causing the people they are supposed to be helping. Only those who adapt and support a healthier, happier future for people and the planet will remain. If we are to survive, the future must be one no longer of power, but of cooperation. Consequently, the increased cannabinoid activity in the human population will ultimately become embedded in the genetics that will stabilize, at least temporarily, Canna sapiens.

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