A tumor is like a condensate, analogous to the precipitation of de-differentiated cells.
Differentiated cells, overcome some kind of energy barrier (Waddingtons epigenetic landscape) and de-differentiate from defined structure to an un-defined mass of cells.
These mass of cells lose their definitive interactions (epithelial mesenchymal transition) and condense to a solid mass.
In the psychology tradition, there are 16 personality types, based on the following characteristic traits in various permutations:
Introversion/Extroversion, Intuitive/Logical, Thinking/Feeling, Judging/Perceiving.
In the yoga tradition, there are three attributes of the mind: Sattva (Calmness/Balance), Rajas (Energy/Activity), Tamas (Dullness/Laziness).
In the Vedanta Tradition there are five sheaths from the depth to the surface: They are annamayakosha (food sheath), pranamayokosha (vital energy sheath), manomayakosha (mind sheath), vigyanmayokosha (intellect sheath), anandamayokosha (bliss sheath).
The three gunas of Sattva, Rajas, Tamas belong to manomayokosha. These three gunas in various permutations are expressed as the personality types.
For example Introversion is correlated with Sattva, Extroversion with Rajas. Clear thinking with Sattva and feeling or emotions with Rajas; Judging with tamas and Perceiving with sattva. Intuitive,Logical both with Sattva.
So an INTP (Introversion, Intuitive, Thinking, Perceiving) personality trait has the predominant qualities of Sattva.
The above-mentioned correlations can be used as a technique for mapping the human mind and its expression as personality traits.
Anaesthetic mediated stilling of brain activity versus non-anaesthetic mediated stillnes
The Prior
- Consciousness expresses itself in and via dynamically functioning neurons.
The floor
of a neuronal cell, consists of microtubules and actin filaments. The
microtubules intercalate to form a dynamically functioning network, that
expands and contracts according to cell activity. This is analogous to sarcomere
filaments in contracting and expanding muscle.
The
expansion and contraction of the microtubule filaments, lead to a rhythmic
oscillation pattern, that manifests itself in a dynamically functioning
neuronal cell, transmitting information via secreted neurotransmitters. In
other words microtubules act upstream of nerve impulse transmission.
When anaesthesia
is administered to a living organism, the anaesthetic treatment locks the
intercalation, inhibiting nerve impulse transmission, resulting in progressive
diminishment of the rhythmic oscillation
pattern of neuronal firing.
This
anaesthesia mediated diminshment of neuronal firing, is different from stillness
acquired through meditation. The anaesthetic treatment physically affects the
neuronal network architecture, which leads to involuntary collapse of the brain.
Meditation is the voluntary stilling of neuronal activity by affecting
neurotransmitter mediated nerve firing, without affecting neuronal
architecture.
We humans possess a Bayesian brain, which implies that our prior memories/experiences/expectations determine our newer experience. It is a pre-conditioned brain that perceives.
This pre-conditioning is partly determined by the free energy principle which states that the difference in free energy between our prior brain states and brain states following the particular experience that is the least, is the one that is selected and retained as an experience/memory. This difference in free energy could be alternatively termed, "minimize surprise".
For further reading:
https://www.youtube.com/watch?v=NIu_dJGyIQI&t=35s
The CD markers (Cluster of Differentiation) pertaining to cells of the immune system, that are on the cell surface are depicted in textbooks in a linear array.
But a cell has a 3-Dimensional geometry. Thus the arrangement of CD markers exhibits topological features, and it is a misnomer to name it as a cluster.Rather name them as differentiation markers, or more specifically, an Array of Differentiation markers (AD markers). This points to a matrix-like arrangement of cell surface markers as compared to a linear array.
Depending on the sequence of connecting the dots, a different network of markers emerge. Similarly, a different set of CD markers on various cell types will have different 3D topological arrangements. This is simiar to a country with different cities lighted up. Cells to Cities ---> FRACTALS.
A Subjective Approach to the Scientific Method
This essay proposes a radical paradigm shift in thinking,
from the traditionally practiced, hypothesis driven- research data collection-research
data analysis driven scientific method, to a richer and more comprehensive
subjective approach to the scientific method. The subjective approach is
proposed to complement and advance the traditional objective approach, in order
to drive scientific research in the direction of asking more insightful
original research questions, develop innovative research methods and implement
more in-depth research data analyses. The
subjective approach aims to address human researcher centered cognitive biases,
in other words anthropocentric cognitive biases.
The premise of the
subjective approach is based on the Indian philosophical inquiry field of Advaita Vedanta (https://en.wikipedia.org/wiki/Advaita_Vedanta
), which in the collected text format is available as the Upanisads (https://en.wikipedia.org/wiki/Upanishads
), and the psychological practice of Raja-Yoga
( https://en.wikipedia.org/wiki/R%C4%81ja_yoga
) which is based on Patanjali’s Yoga Sutras.
For this essay, the philosophical premise of Advaita Vedanta is taken to be the perspective that the world of objects is a world of appearance which is everchanging and impermanent and is superimposed on an underlying all-pervasive substratum, which is the subjective observer. The psychological practice of Raja-Yoga is the intuitive understanding based on yogic experience of the human being as consisting of five koshas i.e.sheaths( https://en.wikipedia.org/wiki/Kosha)superimposing on the individual self, the metaphysical I, which is a witness to the thought process. (Drg Drsya Viveka https://en.wikipedia.org/wiki/D%E1%B9%9Bg-D%E1%B9%9B%C5%9Bya-Viveka ). These sheaths from the outside to the inside are, annamayakosha (food-sheath), pranamayakosha (vital-energy sheath), manomayakosha (mind i.e. recorder of perceptions sheath), vigyanmayakosha (intellect sheath), and anandamayakosha (bliss sheath). The practice of Raja-Yoga which incudes regulation of the prana in the pranamayakosha or vital-energy sheath, regulates the erratic energy flow in the human body where a pre-conditioned mind predominates. A human mind trained by Raja-Yoga practice has balanced energy flow throughout the body, and is going through progressive stages of de-conditioning of priors. Such a deconditioned mind is highly concentrated and is able to provide clearer insights into the objects it gives its attention to. Practioners of Raja-Yoga, do not succumb to erratic and compulsive behaviours, and possess a calm analytical mind as opposed to a reactive mind.
In the following passages I have provided practical
examples of how the practioners of the above philosophical inquiry
method and yogic practice may advance the field of scientific research
investigation, in the areas of: asking
insightful research questions, developing innovative research methods,
implementing in-depth research data analysis, as well as addressing confirmation
bias.
Asking more in-depth original research questions:
A traditional hypothesis and/or data-driven researcher may ask the question, what
is the reason that the leaf of a tree is green. The given answer is the leaf is
green due to the pigment chlorophyll, which drives the photosynthesis process
that manufactures, sugars from carbon dioxide and water in the presence of sunlight. A scientific
researcher well-versed in the Advaita vedantic philosophical inquiry would ask
the question, why does the leaf of a tree appear green to humans, as opposed to
a cat seeing a grey leaf. Does the subject i.e, human perceptive apparatus,
play a role in the outcome of the observation of a leaf appearing green? Is the
green leaf observation an anthropocentric observation?
Implementing more in-depth research methods:
A traditional hypothesis and/or
data-driven researcher may shed light on
the mechanism of how a leaf exchanges energy with its surroundings via
biochemical investigative methods and tools. A scientific researcher
well-versed with Raja-Yoga practice may implement an innovative research method based on the observation that
since both the subject i.e. human observer and the object i.e. the tree,
exchanges energy with the surroundings, why is it that the human subject can
self-regulate its inner vital-energy flow, as well as exchange air with its
surroundings via breath, while a tree is dependent on an outer clean
environment to provide air, sunlight and water to it. An innovative method can
be implemented by such a researcher, who designs a panel of external and internal parameters
that differentially compares energy exchange and flow with respect to the
object i.e. the tree and its environment, the human subject and its environment,
as well as energy flow in the subject-object system i.e. human-tree sub- system
and the human-tree-environment system
In-depth Research Data Analyses: A
traditional hypothesis and/or data-driven researcher may compare the
patterns of similarities and dissimilarities , during bioinformatic analyses of
gene sequences of closely evolutionarily related organisms. A scientific
researcher well-versed in Advaita
vedantic philosophical inquiry would ask whether the patterns of similarities
and/or dissimilarities that appear via
bioinformatic data analyses, are fixed/static or changing as an organism,
adapts to its environment ? If the patterns are changing over time, then what
is the time-scale over which old patterns disappear and new patterns appear?
Thus the research database does not become a fixed entity, but an evolving one.
Addressing human researcher cognitive biases:
A scientific researcher well-versed in Raja-Yoga practice, may question their
own conditioned priors leading to cognitive biases, such as confirmation bias (https://en.wikipedia.org/wiki/Confirmation_bias
). For example if the researcher reads an article that confirms data from their
own laboratory or confirms their hypothesis, since the researchers have evolved
priors via Raja-Yoga practice resulting
in a clearer less conditioned mind, the
researcher may develop in-depth insights into the confirmatory research data or
article and ask insightful original questions which furthers the research
field.
So, from the above examples we can see that a subjective
approach to the scientific method complements the traditional object driven
approach by advancing science from a static body of facts, to an
evolving dynamic entity contingent on
contextual perspectives.
The case for a therapeutic cancer vaccine
RAS proteins are important for normal development. Active RAS drives the growth, proliferation, and migration of cells. In normal cells RAS receives signals and obeys those signals to rapidly switch between the active (GTP) form and the inactive (GDP form) states. Mutated RAS* is stuck in the active state, ignores signals to the contrary, and drives cells to become cancerous.
https://www.cancer.gov/research/key-initiatives/ras/about
Despite repeated attempts, researchers failed to develop a drug that could inhibit the activity of RAS proteins in cancers. They had hoped to find a small molecule that could preferentially bind the unique features of the RAS protein, but they couldn’t find a surface on the protein that would bind a drug.https://www.cancer.gov/research/key-initiatives/ras/about
It is being increasingly recognized that cell signaling is being carried out via phase separation of liquid compartments consisting of the signaling components.
https://pubmed.ncbi.nlm.nih.gov/31792379/
https://pubmed.ncbi.nlm.nih.gov/32203417/
I hypothesize that since, the mutant ras protein is stuck in an active signaling state, there should be a greater number of phase separated droplets in a cell carrying the mutant ras protein versus the wild-type ras protein. An effective drug should be able to inhibit the formation of these phase separated droplets.
In the 2010s, the Shokat Lab at the University of California San Francisco and the Fesik Lab at Vanderbilt University developed innovative drug screening and medicinal chemistry techniques that identified molecules that could bind mutated KRAS proteins. https://www.cancer.gov/research/key-initiatives/ras/about
Rationally designed drugs, may be used to target, matrix metallo-proteinases and collagenases, which are "ENZYMES" that function, to degrade the extracellular substrate in the tumor micro-environment,so as to inhibit cancer cells, escaping from the primary tumor into circulation, to establish secondary metastases. However, such drugs are works in progress.
The case..
Since many challenges exist toward developing effective anti-cancer drugs, another approach would be to develop a therapeutic anti-metastatic cancer vaccine, directed specifically toward the antigen profile of circulating tumor cells, that express altered levels and types of cell-surface biomarkers. The goal would be a multi-epitope anti-metastatic therapeutic cancer vaccine.
Such a vaccine would prevent secondary metastases, since data support the idea that the majority of deaths from solid tumors are caused by metastases. https://pubmed.ncbi.nlm.nih.gov/31397113/
When the drug fails to contain the primary tumor (anti-cancer drug resistance), the anti- metastatic cancer vaccine could prevent the spread of the primary tumor to secondary sites, by targeting tumor cells in circulation.
