Understanding cancer cannot be done on isolated systems. As these Russian dolls, the Matryoshka, which you open only to find a new doll, the question of cancer lead to other fundamental questions. These questions are all related and are linked one to the other.

To find the cure for cancer, you have to understand the very notion of disease. You cannot understand cancer without understanding the other diseases. To understand these diseases, we have to reconsider biological thinking. This leads us to a more fundamental issue: what is life, how does it function? Finally, the last question is the oldest. How was life created on Earth? All these linked questions call for a unifying answer.

Our common thread will be physics and in particular the concept of entropy.

We are all made of star dust. The birth of our universe was the consequence of a terrible explosion named the “Big Bang” by astronomers. The sun burns hydrogen to form helium and heavier atoms. These atoms aggregated to form the planets like the Earth. The first chemical reactions will take place in any watery medium omnipresent on the surface of the earth. A very primitive reaction was water dissociation into hydroxyl radicals on the surface of pyrite-bearing minerals, thanks to the abundant UV-photons created in permanence by the sun. Recombination of such radicals adsorbed on hydrated surface leads to the formation of hydrogen peroxide, H2O2. This process corresponds to very primitive kind of photosynthesis driven by minerals instead of enzymes. This simply stems from the fact that pyrite has a higher entropy content than redox centers buried in sophisticated metallo-enzymes.
Life started long before our sophisticated genome and these primitive chemical reactions still exist. Experts claim that among the first reactions, was the transformation of water into hydrogen peroxide (H2O2 , the active component of oxygenated water) on the surface of pyrite crystals exposed to sunrays. Pyrite rock (or Sulphur, iron, FeS) is rich in divalent iron, an active reducing agent making that reaction possible. Oxygenated water is highly reactive and it will react with simple molecules such as pyruvate to form more complex ones.

These elementary chemical reactions are spontaneous. They predate the appearance of life and do not need genes or enzymes to occur. They are not described in the textbooks and are not considered by modern computer scientists and could explain why their predictions could be dead wrong.

Orgel, L. E. (2008). The implausibility of metabolic cycles on the prebiotic Earth. PLoS Biol, 6(1), e18.

Springsteen, G., Yerabolu, J. R., Nelson, J., Rhea, C. J., Krishnamurthy, R. (2018). Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle. Nature communications, 9(1), 1-8.

 

These reactions predate life. They are still present in our cells. As biologists usually do not have the notion of these spontaneous cycles, they devote special properties to hydrogen peroxide. They therefore speak of signal and growth factor. However, that's just chemistry, free energy transduction and entropy variation.

This also means that free radicals predate life. Using hydrogen peroxyde as a fuel, primitive cycles will be set in motion, will in turn react and form complex molecules.
Springsteen, G., Yerabolu, J. R., Nelson, J., Rhea, C. J., Krishnamurthy, R. (2018). Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle. Nature communications, 9(1), 1-8.

Metabolism predates DNA and proteins. The first requirement allowing spontaneous life apparition on Earth is the existence of a metabolism. It takes the form of thermodynamic cycles able to generate a large output of entropy by degrading low entropy molecular systems (food) into high entropy molecular compounds (waste). Low-entropy molecular systems thus benefit from the large entropy flux generated by such processes. This allows apparition of reduced carbon species such as glucose and soluble phosphates that are observed in any living cell. Life is thus a consequence of the export of entropy. Diseases occur as soon as entropy export mechanisms become impaired.

Henry, M., Schwartz, L. (2019). Entropy export as the driving force of evolution. Substantia, 29-56.

 

Cell growth obeys the laws of physics, like everything around us. The cell cycle is a regulated phenomenon. After dividing, the cell will first increase in size (phase G1). The ions will enter the cell which will grow and then the DNA will duplicate in two (S phase). This is a phase of synthesis, so the mitochondria is at rest.

da Veiga, J., Lafitte, O., & Schwartz, L. (2017). A simple mathematical model for the growth and division of cells. MathematicS In Action, 8 (1), 1-8.

 

The next phase is phase G2. The mitochondria are active and give off entropy in the form of heat. The temperature around the mitochondria is almost 50 degrees. The cell is therefore subjected to a thermal gradient, the interior being warmer than the exterior. The membranes under the effect of the heat flow will ripple and then split in half. Cell division, also called mitosis, is the simple consequence of the increase in temperature given off by the mitochondria. The cell division is only a consequence of the laws of thermodynamics.

Attal, R., Schwartz, L. (2021). Thermally driven fission of Protocells. Biophysical Journal, 120 (18), 3937-3959.

 

Life on Earth seems to originate with the availability of liquid water adsorbed on mineral surfaces, about 4 billion years ago. The first forms of life, the bacteria or prokaryotes appeared about 3,8 billion years ago. Life has known few changes since the beginning. Around two billion years ago, the increasing concentration of oxygen harassed the prokaryotes. They combined with primitive bacteria to form the eukaryotes, the modern cells. The mitochondria is the descendant of these bacteria which entered the primitive eukaryotes. The mitochondria would feed from the eukaryotes. In exchange, they would use the oxygen to burn glucose and get more adenosine triphosphate (ATP). The mitochondria would use oxygen and the cells could breathe. The second revolution took place around 543 million years ago. Collagen appeared probably because of a further rise in the concentration of oxygen.

Saul, J. M., Schwartz, L. (2007). Cancer as a consequence of the rising level of oxygen in the Late Precambrian. Lethaia, 40(3), 211-220.

 

Owing to collagen deposition between the cells, such cells became stuck together. More complex forms of life and animals could form. Within a short period of time, complex life emerged with the «discovery» of the hand, leg, eye and brain. The Burgess Shale is a fossil-bearing deposit exposed in the Canadian Rockies of British Columbia, Canada. It is famous for the exceptional preservation of the soft parts of its fossils. 508 million years old (middle Cambrian), it is one of the earliest fossil beds containing soft-part imprints. A first thought was that anoxic conditions were responsible for the deposition of the Burgess Shale. The anoxic setting not only protects the newly dead organisms from decay, but it also created chemical conditions allowing the preservation of the soft parts of the organisms.

Life is a robust phenomenon with similar concentrations of sodium, potassium and chloride in every living cell from the primitive bacteria to you and me. Moreover, similar lipoproteins constitute the membranes. The same bases constitute the nucleic acids from the very beginning. Every cell consumes low entropy food and releases entropy either in the form of heat or in the form of high entropy molecules.

The second law drives the emergence of life and the evolution from the simple to the complex.

Henry, M., Schwartz, L. (2019). Entropy export as the driving force of evolution. Substantia, 29-56.