Sunday, 18 November 2018

Cancer-Free energy principle

The free energy principle tries to explain how (biological) systems maintain their order (non-equilibrium steady-state) by restricting themselves to a limited number of states.[1] It says that biological systems minimise a free energy functional of their internal states, which entail beliefs about hidden states in their environment. (source wikipedia).

Is it possible that in cancer, during the process of tumorigenesis and metastases the free energy is maximised leading from order to disorder ?

Monday, 12 November 2018


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 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.

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:

Thursday, 1 November 2018

What if:

Each particle is a vibration in a field. Particles interact with each other to give rise to higher orders of emergence.

 What if consciousness/sentience  is the vibration at each level, and interactions of vibrations at higher orders of emergence form complicated structures giving rise to consciousness as manifested through the living brain.

A plant is living and is different from a table made of wood, because the arrangement of atoms is different in a plant versus wood and plant/life interacts with the environment whereas wood does not.

Talking about memories : if they are encoded in the synaptic connections in the brain or within a neuron when the neuron dies the memory dies as structure is lost. But the atoms remain as combinations of vibrations in a field .

What if consciousness is  the vibratory energies at each level of emergence. In higher orders of emergence, vibrations/particles  interact with each other and through phase transition give rise to the brain and mind.

Energy Barrier

Is the directional arrow of time due to an energy barrier ?  Analogy: Uncatalyzed reaction. May be a catalyst-like invention could revers...