Biology is much simpler than it appears. Either the cell breath and burns glucose or it ferments and divide. It snatches electrons and protons of the molecule of glucose to combine them with oxygen to form water. The key chemical reaction of life can be summarized as : 2 protons + 2 electrons + O = H2O.
A human synthesize the equivalent of two glasses of water a day. This is what biologists call metabolic water. To use the language of chemists, protons and electrons are oxidized to form metabolic water. This water is the main constituent of life and we are made up of 70% water. If we look not at the weight but at the number of molecules that make us up, it is 99% water. This is to say the key role of water in biology.
The synthesis of water is the most energetic reaction there is. When engineers want to send a rocket to the moon, the fuel is hydrogen and oxygen. It is the oxidation of hydrogen to form water that will release the rocket from Earth's gravity and send it to the moon. It is the combustion of hydrogen to form water that will keep hydrogen cars running. In order not to explode, the cell must slow down the synthesis of water. So there will be bottlenecks to slow down this reaction and limit energy production.
If water is synthesized harmoniously, the cell will breathe and combine protons, electrons and oxygen to synthesize water. The mitochondria works, the cell breathes, the metabolism is oxidative. Entropy is removed from the body in the form of heat.
If there is an imbalance, for example not enough oxygen, electrons will not be able to combine with oxygen to form water. The mitochondria function poorly, the metabolism is reduced. Entropy is eliminated in the form of molecules and biomass is synthesized.
As the cell burns poorly, it will be a gigantic metabolic traffic jam. Electrons cannot be removed. The body ( made up primarily of water) and it is not conductive. Our electrons will be prisoners of the cell and bind to molecules like NAD or NADP. This is what chemists call a reduced environment.
Diseases are therefore a consequence of the inability of the cell to burn glucose to synthesize water. Electrons, protons and oxygen can no longer unite and be eliminated from the cell as water.
The cell is basically made up of water. This medium is not conductive. Electrons cannot escape from it. Electrons will bind to molecules like NAD to form NADH or NADP to form NADPH. These molecules carry electrons and cause the synthesis of other molecules. It is the excess electrons that are responsible for cell proliferation and the Warburg effect. It is the excess electrons that is responsible for the synthesis of biomass and cell proliferation.
A cell that breathes, oxidizes and eliminates its entropy in the form of heat. A reduced cell proliferates. Biology is that simple. In other words, oxidation is life. The reduction and therefore the excess of electrons are responsible both for growth and therefore reproduction, but also for diseases.
A few decades ago, researchers did not know how to grow cells in Petri dishes, and mice were the main model for biological research. The researcher had an intuition and confirmed, or denied it by testing it on mice. Since then, science has shifted from mice to cells grown in culture and more recently to computer programming. The key reactions are written in a code and analyzed with the help of artificial intelligence.
The researchers need to target the key chemical reactions in order to find effective drugs. There are thousands of computer programs of metabolic flows in normal and cancer cells. To use these programs, the scientist has to write long lines of code, by entering the data from the literature, for example the speed and efficacy of the chemical reactions. Such an approach is problematic, since it narrowly focuses on how chemical reactions are encoded by the genome.
A human cell has around 30,000 genes, some of which code for proteins which play a role in the metabolism. The computer scientist finds these proteins and enters them into his program. The results will guide him to decide which molecule is a reasonable target for the specific drug development being pursued.
Cellular metabolism may seem simple. Partial digestion of glucose (sugar) leads to the formation of two pyruvate ions yielding, in the mitochondria, to the formation of carbon dioxide and water. A computer program can therefore be written, considering the glycolysis step (degradation of sugar into pyruvate) followed by the combustion of the latter in the mitochondria.
These computer models are wrong, because several key reactions are missing. Our cells live in an atmosphere rich in oxygen. Cellular machinery uses this gas for combustion. The programs only take into account the reactions involving oxygen. They do not pay attention to the reaction caused by the free radicals.
Life appeared at a time when there was hardly any oxygen in the air. Accumulation of the dioxygen gas in the atmosphere had to wait for about two billion years, the time necessary for the algae to release sufficient quantities in the atmosphere.
The very reason for the Warburg effect: excess electrons
For nearly a century, biologists have known how to cultivate both cancer and normal cells. The cell is placed in a Petri dish covered with a liquid rich in sugar with 5 or 10% fetal calf serum. Blood is taken from the newly delivered fetus at slaughterhouses and the serum is extracted. This serum is rich in proteins and allows the growth of the cell which is incubated at 37 degrees in an atmosphere rich in 5% CO2 and 20% oxygen. The cell will grow and then divide and form colonies. These cultivation techniques have been standardized and are now universal. They are different from life in the real world of our body. In living organisms, the oxygen content is much lower because oxygen diffuses poorly in the tissues and especially the proteins that our cells can digest are not of fetal origin. But in a Petri dish, if you expose the cells to adult serum, or to lower levels of oxygen, they will divide much more slowly. Which would slow down research….
At the beginning of the 20th century, a dogma appeared. The normal state of a cell is quiescence. The normal cell does not divide. It is only because it is ordered to do so that the cell will divide and proliferate. An example are the growth factors. A patient has anemia, for example following chemotherapy. The multiplication of red blood cells has been blocked by drugs that target cancer. The patient is pale and has difficulty breathing. The doctor injects a protein, a growth factor that will tell the blood cells to multiply. These are the same growth factors that are bought, illegally, by athletes in search of performance. Their blood will carry more oxygen to the muscles and they will run quicker.
In reality, these proteins are not growth factors , but inducers of differentiation. Red blood cells are made by the same stem cells as white blood cells or platelets. These "growth" factors will direct the production of stem cells to red blood cells and slow down those of white blood cells or platelets. They will increase the number of red blood cells but decrease the number of white blood cells or platelets.
Well-nourished cell will divide. The cell doesn't need a signal for that. Growth is the normal state of the cell.
Sonnenschein, C., & Soto, A. M. (2008, October). Theories of carcinogenesis: an emerging perspective. In Seminars in cancer biology (Vol. 18, No. 5, pp. 372-377). Academic Press.
We have drawn up and demonstrated a fairly simple picture. The excess electrons cause the synthesis of biomass. The rest is automatic. The cell grows bigger and the temperature gradient generated pushes the cell to divide into two daughter cells.
One final question remains, the origin of the Warburg effect. Otto Warburg, demonstrates that cancerous fermentation is irreversible. The cell is blocked in synthesis and can no longer breathe, even in the presence of oxygen.
Warburg, O. (1956). On respiratory impairment in cancer cells. Science, 124 (3215), 269-270.
In the diseased cell, oxygen cannot oxidize the electrons and protons torn from the glucose. This will result in what many call oxidative stress. The oxygen will bind to other targets, especially proteins. These proteins will be oxidized and inactivated. The demonstration can be seen in the mirror. Over the years, the hair becomes lighter and whiter. When a teenager has white hair, he has used an oxidant. Oxidation of the hair changes its color which turns white. In the elderly, hair lightening is the consequence of this oxygen which no longer finds its target in the mitochondria and which therefore will oxidize the proteins of the hair.
Krisko, A., Radman, M. (2019). Protein damage, aging and age-related diseases. Open biology, 9 (3), 180249.
Slade, D., Radman, M. (2011). Oxidative stress resistance in Deinococcus radiodurans. Microbiology and molecular biology reviews, 75 (1), 133-191.
Oxygen atoms and electrons will also react with the ubiquitous molecules of water to form free radicals.
One notion is omnipresent in biology, that of free radicals. It emerged in the 1950s, when chemists from the petroleum industry became interested in biology. Today, for many, free radicals are a key to biology but also to disease. Cancer but also aging or Alzheimer's disease are said to be a consequence of the excess of free radicals. The idea widely conveyed by the mainstream press is that these radicals are toxic and responsible for all evils. Like all dogmas, they must be reviewed from the perspective of real science.
Free radicals are not the villains so much described in popular literature. They are extremely reactive molecules that are the source of life. Life began long before our sophisticated genome, and these primitive chemical reactions still exist. Experts say one of the first reactions is the transformation of water into hydrogen peroxide (H2O2, or hydrogen peroxide) on the surface of pyrite crystals exposed to sunlight. Hydrogen peroxide is very reactive and it reacts with simple molecules such as pyruvate to form more complex molecules.
So life began with the action of free radicals. These elementary chemical reactions are spontaneous. They predate the onset of life and do not need genes or enzymes to occur. They are not described in textbooks and are not considered by modern computer scientists, which could explain why so much of their modeling is 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.
The normal cell breaks down hydrogen peroxide into water by a specialized enzyme called catalase. In a normal cell, electrons bind to oxygen and hydrogen to form water. The deterioration of this reaction in cancer cells leads to the creation of active oxygen compounds such as hydrogen peroxide. These reactions, prior to life, will therefore take place. Since biologists generally do not understand these spontaneous cycles, they attribute special properties to hydrogen peroxide. They therefore speak of signal and growth factor. However, this is all just chemistry and entropy variation.
Hachiya, M., Akashi, M. (2005). Catalase regulates cell growth in HL60 human promyelocytic cells: evidence for growth regulation by H2O2. Radiation Research, 163 (3), 271-282.
The idea that drives us is that these free radicals will stimulate cell growth and will cause this limitless growth called cancer.