Adaptation

Are humans sculpting their environment leading to adaptation and inheritance of adapted traits ? 

Emergent Properties in Biology-Interactions

I am writing this blog post to connect the ideas of emergence with what we know in biology.

"Interactions" leading to emergent properties, such as the phenotype of an organism, which emerges from the genotype of the organism is where biology research is heading to.

The genotype is encoded in the DNA of the organism which through the transcriptional and translational machinery gets converted into proteins. These proteins interact with each other in signal transduction networks which consist of positive and negative feedback loops. It is these signaling networks that convey the signal from outside a cell to the functionality of the cell. 

On the other hand, the proteins interact with the DNA and can regulate switching on/off of genes via epigenetic mechanisms.

 So in a cell, there are  "layers of interactions", where each layer instructs the subsequent layer, and the functional property of the cell emerges from the genotype. The layers of  cellular processes  are epigenetic regulation--->transcription--->translation--->signaling networks --->feedback loops thus forming a complete circuit. 

The cells interact with each other forming tissue and with increasing scales of interactions the organ emerges, followed by the organ system and then the whole body. Thus phenotype emerges from genotype.

 The body of the living organism then interacts with the environment and what emerges is the ecosystem of complex interactions which form a part of the biosphere on earth. Each emergent layer consists of a multitude of interactions, which when increased on the scale gives rise to the next emergent layer which is more complex than the previous layer.

 Thus interactions are fundamental to emergence and form the glue of the living world.

Cancer , Entropy , Pendulum model of Cancer

I have written the following blog post and pinned it so that cancer researchers  who may come across this blog post can get ideas about why cancer occurs, how to think about cellular states in tumor formation and how they relate to the driver mutations and the tumor microenvironment. Hope it is useful.

The risk of developing cancer increases with age. The probabilities of errors in replication resulting in cancer causing mutation  occur because of the second law of thermodynamics . Error in DNA replication implies,"wrong bases", imprecisely inserted in the DNA resulting in many alternate ways of structural re-organization. This is exactly what the second law of thermodynamics predicts- an increase in entropyof the universe. With age the human dies, loss of physical organization of the human body occurs, matter gets converted to energy, and energy is returned back to the universe.

So for treatment of cancer local entropy has to be decreased, in other words there has to be a constrain on structural organization, to regain back organization/precision accuracy. This means drugs have to be discovered/designed /invented that decrease entropy/randomness/disorganization of the system in this case the malignant tumor.

Humans are only following the laws of physics. Elephants do not get cancer. They have multiple copies of the tumor suppressor p53. Their metabolism is slow  resulting in large body size, and very long life spans. Lower metabolic rates means slower reactions and lower entropy. Humans unlike elephants have high rates of metabolism and accumulate toxic by-products. These contribute to errors in DNA replication which results in diseases such as cancer and the   aging process.

Probably high metabolism rates  is related to advanced cognitive capacities. Elephants may live longer , do not have cancer but they lack cognitive capacity comparable to humans . It is this cognitive capacity  which has allowed humans to adapt themselves to the surroundings and influence their environment including climate. Maybe this advanced cognitive capacity will help design useful anti cancer drugs.

Tumor heterogeneity hypothesis-Different tumor cells possess altered ratios of tumor suppressing to tumor promoting activity, resulting in altered  signaling networks in different cells.

Cancer occurs when there is impairement in restoration of homeostasis due to 2nd hit which is microenvironment related,  in primary mutational hit (tumor suppressor inhibiting/oncogene activating) cells.

Sequence of events-Ist mutational hit. Cells starts dividing and at the same time  retains homeostatic balance, so they form a benign tumor. Second hit occurs (tumor microenvironment interactions in which cells in the microenvironment lacking the mutation i.e. the soil fails to  contain the dividing cells as they lack the primary mutation, and give insufficient inhibitory signals to the dividing cells) -Homeostasis breaks down, malignant Tumorigenesis results.

Visualization-Oscillating pendulum

Cellular states preceding and following tumorigenesis are  like- an oscillating pendulum that  overshoots mean position once (equivalent to cellular state i.e benign tumor after primary mutational hit). The pendulum tries to  come back to mean balance position (equivalent to restoring homeostasis in cell after primary mutational hit). Due to  loss of elasticity of pendulum string (equivalent to secondary hit due to tumor microenvironment interactions) status quo of extreme position maintained, (which is  equivalent to malignant tumor ).

Proposed Mechanism for the above:

What if the default mode of single cells is replication and differentiation/ maturation is secondary. Depending upon the interaction of replicating cells with the microenvironment, adjacent cells release inhibitory molecules which make a replicating cell differentiate/mature. This is because competition for food resources as a whole will wipe out cells, so for survival cells divide to a certain number and differentiate, so that the tissue survives as a whole.

 In cancer the default replication of cells carrying driver mutations for tumorigenesis  is not inhibited sufficiently by the surrounding cells so uncontrolled cell proliferation occurs. It is possible that driver mutations arise all the time in cells due to replication errors, but then such cells do not survive and proliferate because inhibitory signals by  surrounding cells  impedes their survival to allow tissue/organ/host  formation to occur. This results in a benign tumor.

In malignant tumorigenesis the tumor survives at the expense of a host, because the cells in the neighbouring microenvironment of the cell carrying the driver mutation are not able to give out sufficient inhibitory  signals to inhibit proliferation of cells carrying the driver mutation. One reason could be that a sufficient number of neighbouring cells lacking the driver mutation is needed to give out sufficient signals to inhibit proliferation of cells lacking the driver mutation. If cells lacking the driver mutation divide at a slower rate than cells with the driver mutation, then they will not be able to provide sufficient inhibitory signal against the cell carrying the driver mutation, resulting in  a malignant tumor.

Activating a tumor suppressor/inhibiting an oncogene within a tumor by a drug may alter tumor cellular state. Tumor cells may adapt and give survival cues to the tumor microenvironment. So drug has to target signaling by tumor microenvironment to tumor cells. So not one drug but two, targeting tumor cell +tumor microenvironment.

I found the following articles particularly useful:
http://www.pnas.org/content/111/48/17188.full
http://www.physiology.org/doi/full/10.1152/ajpcell.00145.2015
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891444/

Meditation-Based on Experience

The Rishis (Sages) of the past meditated. They included both men (eg Kapila) and women (eg Gargi).
By meditate I mean concentrated focus/observation of their own psychical system.
Meditation is a systems approach.  The rishis went from the surface layers of the mind to probe into deeper levels.  The body is multicellular , including the brain (consisting of the sensory input processing system). Under normal circumstances, in a conditioned human, the physical predominates i.e data arriving from the sense organs (eyes, ears etc) .The  4 components i.e.buddhi-intellect ahamkara-identity/individualization capacity, manas - memory bank , chitta-(awareness at the mental level)are a  prakriti (psychical nature) according to sankhya psychology. The 3 attributes of sattva(balance/equilibrium/harmony),rajas (activity) and tamas (inertia) are present in various combination in each individual human. The observable universe is when the self/atman/purusha/subject/observer/ is superimposed by prakriti.During meditation, the self /atman/purusha/observer loses superimposition of  prakriti in the following manner.  When prakriti is stilled by various techniques like mantra repitition, meditative techniques of raja yoga/patanjali yoga  the observing part (subject/atman) has no more object to observe. Subject-object become one. When the atman/self/purusha/subject/observer  loses identification with the object, (distinct energy fields lose their individual vibrations=detachment in gita where kshetra=field and kshetrajna=knower of the field) the self/atman merges (unite/integrate=yoga) into the underlying unified energy field (brahman) . Thus tat tvam asi. Atman (Individual self-You-tvam) =Brahman (universal-Tat). Emergent consciousness is lost i.e vibrating energy fields is lost and equilibriated/bliss energy fields remain. This is the result of meditation.
Terminology in Advaita(Non-dual)=Atman (Individual Self), Brahman (Universal Self).
Terminology in Sankhya =Buddhi (Intellect), Ahankara (identity), Chitta (mental awareness), Manas (memory bank), Sattva (Balance), Rajas (Activity), Tamas (Inertia).
Terminology in Gita =Kshetra (Field), Kshetragna (Knower of the Field)
Deities-Anthropomorphic representation of abstract attributes.
The various deities of "hinduism" represent various abstract mental states during subject object split. For eg. Shiva represents destruction (Tamas), Vishnu-preservation (Sattva)-Brahma-projection/creation (Rajas) of the universe .This is because prakriti engages in creative, maintaining and destructive activities.
4 experience based paths to the above:Bhakti-Yoga(Love of Self-subject object separation followed by subject object unity), Karma -Yoga (Work /Activity based, Removing focus from fruits of activity but focusing on the activity itself, love of work and work for the sake of work and not for the gains or losses/side effects that accrues with it  ), Raja-Yoga( Patanjali's Ashtanga Yoga System-involves dhyana,dharana,samadhi), Jnana-Yoga(Knower of Self/Advaita based).
Christ who experienced unity is quoted as -do unto others as you would like others to do unto yourself was a bhakta (lover of the self). Buddha was a jnani (knowledge seeker) (meditated on the self).
Loss of  organization  at the physical level/structure =death of the body.
Aging = loss of structure/physical organization.
"God" in "Hinduism"=Atman/IndividualizedSelf which merges into Universal self"Brahman".
Good (Sattv-ic)/Evil (Tamas-ic)=Creative/Destructive mental energy states.
Self knowledge= Atman knowledge

advaita vedanta

Advaita Vedanta's rejection of theism is a consequence of its insistence that “Brahman [ultimate reality] is without parts or attributes…one without a second.” (Shankara [traditional attribution], second half of the 8th century: 101) If the Brahman has no properties, it necessarily lacks the properties of omniscience, perfect goodness, omnipotence, and personhood, and cannot therefore be understood as God.

https://plato.stanford.edu/entries/concepts-god/

Naturalism in the Ancient Times

Ref: https://plato.stanford.edu/entries/naturalism-india/

The phenomenal world-A human sees a green leaf. A cat sees a grey leaf. Thus the phenomenal world of experience is a function of the genetic system of  a particular biological species. It is impermanent according to advaita vedanta adherents or advaitins , since it changes from one species to another.

Advaitins ascribe to the "universal conscious principle" underlying it all. To my mind the first thing that comes with the word "universal" in the light of present day  theories in the realm of scientific investigation are "entangled energy fields", which vibrate to give rise to particles, which interact to give rise to higher orders of emergence. 

The word "conscious" implies in normal terms "aware". How can energy fields be aware. Awareness arises from emergence. 

The word "chit" of sanskrit has been "translated" to consciousness/awareness. "Chit"means "being"/ presence". So "Brahman" the universal energy field is universal presence, which when confined to an individual "living species" is the individual emergent self/ "atman". What advaita claims-through the experience of meditation, when the mind calms/settles down, is Atman=Brahman. 

 To me it implies there is resonance between the energy fields of Brahman and Atman.

 This reminds me of the concept of fractals:

1. "a curve or geometrical figure, each part of which has the same statistical character as the whole. They are useful in modelling structures (such as snowflakes) in which similar patterns recur at progressively smaller scales, and in describing partly random or chaotic phenomena such as crystal growth and galaxy formation".
2. 
   
3. Resonance occurs if Brahman and Atman are at the same frequency. This can occur if the individual emergent self (Atman) is a fractal part of  the underlying universal energy field (Brahman). The postulated mechanism is as follows : The smaller fractal part - Atman resonates with the whole-Brahman, at the same frequency but has a larger amplitude. On the whole the predicted frequency is very low as this occurs during a calm mental state. As the Atman loses the "rough edges"of  fractal complexity  it begins to  resemble the simpler near equilibrium universal energy field- Brahman.
4. . 
5. 
   

Meditation (there are many types and levels of depth) gives an altered view of reality as the attributes of the mind changes. A non-meditator has an comparatively unsettled/more vibratory mind while a meditator having a calmer mind reflects Brahman.  Hence the conclusion by advaitins is that the phenomenal world is an experience of the unsettled mind, hence individual identity/vibrations i.e ahamkara , intellect i.e buddhi, manas i.e memory bank/impressions  and chitta i.e being limited by identity arises. In Yoga psychology these 4 form the nature of the mind/prakriti and atman/purusha, is enveloped by prakriti.

Nivritti (Moving inwards via meditation from the outward environmental experience of the world towards the inward self i.e. Atman and further into Brahman) is an inward process towards simplicity. Eg. as practised by the advaitin/non-dual energy oriented naturalists.

Pravritti (Moving outwards towards the environment  via physical and mental work) is an outward process of the self/Atman towards complexity. Eg. as practised by  the atomists/materialist naturalists Carvakas.

 Pravritti is a  complex process towards outward fractal complexity and functions through cogitation/intelligence. This in in contrast with  the simpler process towards inner  fractal simplicity i.e.  Nivritti  which functions through non-cogitation/meditative processes.

Hence the Carvakas who consider the world of experience to be real/final  are atomists. Thus under Western context of naturalism which implies physical nature, Carvakas are true naturalists in their epistemology (mechanism) and ontology (being) while advaitins are naturalists in their epistemology but not in their ontology. 

 In other schools of vedanta i.e dvaita school Brahman has being equated to or having a reflection in the ishvara/antaryamin/inner controller (God), which can be anthropomorphised and worshipped as in Hinduism. 

Cancer-Laws of thermodynamics-Oscillating between states -Involvement of Driver Mutations/Tumor Microenvironment

I have written the following blog post and pinned it so that cancer researchers  who may come across this blog post can get ideas about why cancer occurs, how to think about cellular states in tumor formation and how they relate to the driver mutations and the tumor microenvironment. Hope it is useful.

Cancer accelerates extended life span to death and therefore its frequency arises with age. The probabilities of errors in replication resulting in cancer causing mutation  occur because of the second law of thermodynamics . Error in DNA replication implies lack of  precision/accuracy in replication and an increase in randomness. This is exactly what the second law of thermodynamics predicts- an increase in entropy i.e randomness of the universe. With age the human dies, loss of physical organization of the human body occurs, matter gets converted to energy, and energy is returned back to the universe.

So for treatment of cancer local entropy has to be decreased to regain back organization/precision accuracy. This means drugs have to be discovered/designed /invented that decrease entropy/randomness/disorganization of the system in this case the malignant tumor.

Humans are only following the laws of physics. Elephants do not get cancer. They have multiple copies of the tumor suppressor p53. Their metabolism is slow  resulting in large body size, and very long life spans. Lower metabolic rates means slower reactions and lower entropy. Humans unlike elephants have high rates of metabolism and accumulate toxic by-products. These contribute to errors in DNA replication which results in diseases such as cancer and the   aging process.

Probably high metabolism rates  is related to advanced cognitive capacities. Elephants may live longer , do not have cancer but they lack cognitive capacity comparable to humans . It is this cognitive capacity  which has allowed humans to adapt themselves to the surroundings and influence their environment including climate. Maybe this advanced cognitive capacity will help design useful anti cancer drugs.

Tumor heterogeneity hypothesis-Different tumor cells possess altered ratios of tumor suppressing to tumor promoting activity, resulting in altered  signaling networks in different cells.

Cancer occurs when there is impairement in restoration of homeostasis due to 2nd hit which is microenvironment related,  in primary mutational hit (tumor suppressor inhibiting/oncogene activating) cells.

Sequence of events-Ist mutational hit. Cells starts dividing and at the same time  retains homeostatic balance, so they form a benign tumor. Second hit occurs (tumor microenvironment interactions in which cells in the microenvironment lacking the mutation i.e. the soil fails to  contain the dividing cells as they lack the primary mutation, and give insufficient inhibitory signals to the dividing cells) -Homeostasis breaks down, malignant Tumorigenesis results.

Visualization-Oscillating pendulum

Cellular states preceding and following tumorigenesis are  like- an oscillating pendulum that  overshoots mean position once (equivalent to cellular state i.e benign tumor after primary mutational hit). The pendulum tries to  come back to mean balance position (equivalent to restoring homeostasis in cell after primary mutational hit). Due to  loss of elasticity of pendulum string (equivalent to secondary hit due to tumor microenvironment interactions) status quo of extreme position maintained, (which is  equivalent to malignant tumor ).

Proposed Mechanism for the above:

What if the default mode of single cells is replication and differentiation/ maturation is secondary. Depending upon the interaction of replicating cells with the microenvironment, adjacent cells release inhibitory molecules which make a replicating cell differentiate/mature. This is because competition for food resources as a whole will wipe out cells, so for survival cells divide to a certain number and differentiate, so that the tissue survives as a whole.

 In cancer the default replication of cells carrying driver mutations for tumorigenesis  is not inhibited sufficiently by the surrounding cells so uncontrolled cell proliferation occurs. It is possible that driver mutations arise all the time in cells due to replication errors, but then such cells do not survive and proliferate because inhibitory signals by  surrounding cells  impedes their survival to allow tissue/organ/host  formation to occur. This results in a benign tumor.

In malignant tumorigenesis the tumor survives at the expense of a host, because the cells in the neighbouring microenvironment of the cell carrying the driver mutation are not able to give out sufficient inhibitory  signals to inhibit proliferation of cells carrying the driver mutation. One reason could be that a sufficient number of neighbouring cells lacking the driver mutation is needed to give out sufficient signals to inhibit proliferation of cells lacking the driver mutation. If cells lacking the driver mutation divide at a slower rate than cells with the driver mutation, then they will not be able to provide sufficient inhibitory signal against the cell carrying the driver mutation, resulting in  a malignant tumor.

I found the following articles particularly useful:
http://www.pnas.org/content/111/48/17188.full
http://www.physiology.org/doi/full/10.1152/ajpcell.00145.2015
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891444/