Visual comparison of Falsifiability & Neti Neti

 

Falsifiability & Neti Neti

 

Falsifiability and Neti Neti

In the field of the Science of Philosophy, Karl Popper proposed the theory of Falsifiability. Basically one comes to scientific truths , when theories are proven false, and whatever survives the false theories is taken to be the scientific truth. This is the method of evolution of scientific facts.

This reminds me of the “Neti Neti” method of getting to the subjective from the objective via negating what is being observed, as the “Not I” to what is remaining as the Ï”or Self , which is clearly mapped out in the Advaitic Vedantic text: “Drg Drsya Viveka”. The text title  is loosely translated as illumination by: neti neti of Drsya(what is observed) by the the Drg-the witnessing I/seer . 

  

Targeting Cancer Stem Cells

 Targeting Cancer Stem Cells

From Takahashi and Yamanaka, Cell 2006,   Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers”.”

 

Nude mice are deficient in the the immune system, so they allowed tumor formation by iPS cells and did not attack them. This observation indicated that when mature differentiated cells like fibroblasts which have specific functions, de-differentiate to immature pluripotent stem cells, they magnify the property of self-renewal and skew towards uncontrolled self-proliferation as opposed to differentiation. This indicates that tumor formation could be initiated by de-differentiated cells, where signaling pathway activity regulating self-renewal is amplified. Such cells called cancer stem cells could be exploited as targets for cancer therapy, as these signnaling pathways have basal activity in normal stem cells and are amplified in cancer stem cells. One such signaling pathway is the Wnt-beta catenin signaling pathway which promotes cancer stemness. For example Beta-catenin inhibitors are experimental cancer treatments currently being evaluated in early-phase clinical trials, focusing primarily on agents like tegavivint and FOG-001. There are currently no FDA-approved drugs that directly target the Wnt/β-catenin pathway due to challenges with toxicity and the complexity of cellular adhesion.atenin inhibitors are being tested in clinical trials. So alternate molecules in the cancer stem cell signaling pathways need to be validated as targets for cancer stem cell therapy.

Is a Synthetic Cell the same as Synthetic Life ?

 

From  a bioRxiv preprint , “Here we demonstrate a complete cell cycle for a synthetic cell undergoing selection, with genome replication, growth, resource acquisition via feeding, and genetically encoded division” from “A Chemically Defined Synthetic Cell Capable Of Growth And Replication”, Gaut et al., 2026.

Link: https://www.biorxiv.org/content/10.64898/2026.07.01.735724v1#:~:text=Here%20we%20demonstrate%20a%20complete,feeding%2C%20and%20genetically%20encoded%20division

The question I ask is a synthetic cell =synthetic life ? The answer is a resounding no. The hallmark of biological organisms, higher up the hierarchy of the tree of life is multicellularity followed by self-organization. Single cells survive in specific environments and are more primitive. So until the single cell shows potential for multicellularity and organization into colonies,clusters,tissues, it will be a bottleneck for synthesizing “living organisms” from scratch.

During the synthesis of  an artificial cell, it remains to be seen, that information coded in the molecular components or sub-structures sufficient for the derivation of a cell in a fluid environment; or does information encoded in the environment required ? A cell develops in a fluid environment as its cytoplasm is gel-like and not in a solid such as sand. Presumably, mobility of molecular components occur in a fluid. Maybe exchange of  information encoded in molecular components and the fluid environment via molecule-environment interactions lead to the emergence of a cell. The environment then becomes indispensable for higher-order organization. So under controlled laboratory conditions, the milieu for organization of cells into higher-order living structures, could be derived from natural environments such as  wetlands, marshes, hydrothermal vents as they will encode the environmental information.

Does Cancer Metastasis Occur via a Quorum-Sensing-Like Mechanism?

 

Does Cancer Metastasis Occur via a Quorum-Sensing-Like Mechanism?

 

In February, The Hindu published an article titled “Bacteria Can Talk to Each Other and Are Multilingual, Says Biologist.” The biologist in question is Bonnie Bassler, who runs a laboratory at Princeton University and has spent her career studying a process called quorum sensing in bacteria. Quorum sensing is the mechanism by which bacteria communicate and coordinate group behavior based on population density. They do this by continuously secreting and detecting chemical signaling molecules known as autoinducers. Once the bacterial population reaches a critical threshold, the resulting concentration of autoinducers triggers the synchronized activation of specific genes.

After listening to a conversation with Bassler on physicist Sean Carroll's podcast, Mindscape, I found myself wondering whether metastasis — the spread of cancer to distant organs — might occur through a similar, quorum-sensing-like mechanism.

Metastasis involves a step called the epithelial-to-mesenchymal transition (EMT), in which stationary, polarized epithelial cells lose their cell-to-cell adhesion and acquire migratory, invasive properties, becoming mesenchymal cells. This same process also plays a crucial role in embryonic development and wound healing. Within the primary tumor, cells proliferate uncontrollably and secrete enzymes called matrix metalloproteinases (MMPs), such as MMP2 and MMP9. These enzymes initiate and sustain EMT by breaking down basement membranes, degrading adhesion molecules like E-cadherin, and releasing pro-EMT signaling factors such as TGF-β from the extracellular matrix. Together, these actions drive cancer invasion and metastasis.

If quorum sensing is indeed involved in EMT, it may work as follows: in the primary tumor, cells divide uncontrollably and release MMPs, which act much like autoinducers. As the tumor cells multiply, MMP concentration rises in step with them, and once the tumor reaches a critical size, this rising concentration of MMPs triggers the synchronized activation of EMT genes. This remains a hypothesis, however, and would need to be tested directly in primary tumor cells through wet-lab experiments in tissue culture.

How Advaita Vedanta validates Many worlds interpretation of Quantum Mechanics

 How Advaita Vedanta validates Many worlds interpretation of Quantum Mechanics

In Advaita Vedanta (non-dualism) practise, when the ego construct dissolves via Yogic practices or meditation, the experience of Self  (Atman) localized to the individual is now experienced in the absence of individuality i.e. no separation from other living or non-living beings in the universe. This non-individual experience is termed Brahman-a vast infinite still field of potentialities .

In the  quantum mechanics when a measurement occurs a wave is observed as a particle. The wave is a field of potentialities and the wave function is a mathematical description of a physical system defining the probability amplitude of a particles’ probabilities. According to the many-worlds interpretation, during a measurement all possible outcomes of a quantum event occur in its own distinct universe, but the observed outcome is experienced in one universe. This measurement outcome is  similar   to the experience of a localized self i.e the atman, which is actually a part of all possible outcomes which can occur only in a field of infinite possibilities or Brahman.

The difference between Advaita Vedanta and the Many worlds interpretation of quantum mechanics is that Brahman as a field of infinite possibilities/potentialities is Self-Aware, while Many Worlds does not make any such statement.

Cancer-A story of condensates, feedback loops and the epigenome ?

 

Cancer_Hypothesis

1.Probably the epigenome of a cell is modified by an oncogenic mutation. Phenotypic plasticity/tumor heterogeneity occurs in this process.

2. This modified epigenome overrides the inhibitory signaling of tumor microenvironment via activating stemness networks. Chaos ensues.

3. The above (2) breaks cell cell interactions leading to tumor cells release from primary site and spread i.e. invasion.

4. Altered epigenome leads to epithelial mesenchymal transition.

5. Tumor cells at secondary site  undergo mesenchymal epithelial transition due to restored epigenome in a new microenvironment.

6. As critical threshold of oncogenic protein/signaling activity is breached (1) happens again.

7. A vicious cycle of tumor growth and spread ensues.

8. Altered expression/phenotype of tumor cells  containing oncogenic mutation occurs via phase transition. Mutant oncogenic proteins form multiple aggregates with their target sustrates forming numerous biomolecular condensates. Sustained oncogenic signaling occurs in biomolecular condensates which are resistant to negative feedback loops.  Membranes of such biomolecular condensates could prevent access of inhibitors to oncogenic signaling. This sustained signaling acts like a siren activating stress response pathways. Such stress response pathways could activate suppressive epigenomic enzymes in a negative feedback loop. The reason being that suppressive epigenomic enzymes such as histone deacetylases can suppress both tumor suppressor and oncogene transcription, but in a tumor it is the tumor suppressor that is silenced, but not the mutant oncogene levels. Ultimately it is cell survival regulating these feedback loops.

9. Since, the unpredictable component is how the epigenome is altered from a normal one to a cancerous one via the  oncogenic mutation,the oncogenic mutation via aberrant signaling could downregulate promoter activity of tumor suppressors via activating suppressive epigenome enzymes  like methylases.  The oncogenic mutation re-inforces its own activity positively since although the promoter of the mutant oncogene can be silenced by methylation, the methyl groups at promoters of mutant oncogenes are removed by demethylases as cell survival is the ultimate goal.

Stemness plays a role when downregulation of a tumor suppressor activates the uncontrolled  self-renewal activity of stemness networks, probably by activating oncogenic transcription factors of stemness networks that function in self-renewal.

The analogy with an Enzymatic Reaction:

Initiator-Oncogenic mutation, Epigenome alteration/Ist hit

Catalyst-Altered Tumor Microenvironment /2nd hit