The first forms of life on Earth were single-cell organisms: bacteria and archaea. They lived in oceans to escape UV radiation at a time when there was no free oxygen in the atmosphere.
These were fairly simple entities that had genetic programs tightly packed—gene next to gene—in short RNA or DNA strands floating freely within a cell. The genetic material had to be short because there was no ozone layer in the atmosphere, and longer strands would be more vulnerable to UV radiation reaching Earth’s surface.
The genetic program contained recipes for proteins necessary for the cell to function. The entire cellular machinery needed energy to work. The energy was taken from the outside world through the cell’s surface, in the form of chemical compounds. This food would be processed inside the cell without involving oxygen. For example, glucose would be taken inside the cell and fermented in the process called glycolysis to produce about two net energy units stored in two ATPs.
The prevalent shape of the cells was spherical. There were a couple of reasons for that. Firstly, a cell’s interior has a different chemical composition than the outside, and an osmotic pressure builds up inside the cell in most environments.
That pressure is best handled by a spherical cell membrane that keeps it mechanically stable. The membrane itself is energetically costly. The spherical shape gives the best volume-to-surface ratio.
After a billion years of evolution, another source of energy was utilized: sunlight. First, cyanobacteria developed chlorophyll-based photosynthesis that converted carbon dioxide and water into glucose molecules directly inside the cells with the energy harvested from ambient light. As a side product of photosynthesis, six molecules of oxygen were produced per each new glucose molecule.
Whether it was chemical compounds or light, they all had to cross the cell’s surface to be used as an energy source for this early life. That imposed a limit on cell size. Since food or radiation needed to cross the cell’s membrane, the larger the cell’s diameter, the more food could be delivered.
However, the energy requirements for the cell scaled proportionally to the cell’s volume, as all the chemical processes occurred uniformly within the cell body.
Clearly, the surface of a spherical shape is proportional to the radius squared, while the volume goes with the radius cubed.
That means that the energy needs quickly exceed possible diffusive influx of food into the cell. Thus, a size limit of early organisms was set at single-digit micrometer range.
For that reason, if a cell encountered a new rich food source, it could not grow much to devour it before competition. The only available strategy was to multiply into similar-sized cells to promote survival of the species. Thus, the organisms that developed that strategy in their genetic software outcompeted all others.
The buildup of toxic oxygen in the atmosphere spelled disaster for most of the organisms. The Great Oxygenation Event 2.4 billion years ago was the first known mass extinction phenomenon.
Some bacteria survived it by utilizing oxygen in processing food at much higher efficiency than fermentation. The efficiency jumped from 2 ATPs per glucose molecule to about 34 ATPs.
Moreover, the energy gain did not require an increase in the external surface of the bacteria. It was maintained by a series of electron transfers facilitated by internal bacterium surface (cristae) that could be folded in a fixed small overall volume!
Those bacteria were symbiotically incorporated in numbers within other single-cell organisms and formed early mitochondria, the first cell’s organelles. Mitochondria gave over a tenfold increase in energy available to the cell from a single glucose molecule. That meant that the size of the cell could increase dramatically. The ozone layer developed from oxygen around the Earth’s atmosphere blocked most of the UV radiation. That in turn lifted the size limit on the DNA for organisms closer to the water surface, and more light could be used for photosynthesis. Now DNA could be much longer, and the program it contained could be more complex. The genes are no longer tightly packed, and some new regulatory mechanisms can be introduced to DNA.
First of all, it was crucial to maintain high food-processing efficiency so as not to waste any energy. That is why control mechanisms were embedded in the DNA to prevent cells from stopping at glucose fermentation, and the fermentation products were delivered to mitochondria for the oxygen-assisted processing.
The longer DNA strand needed better organization and protection than just a free-floating strand. The cell’s nucleus engulfing the DNA showed up as a new organelle, and the eukaryota cells were born.
Another benefit of longer DNA and more sophisticated regulation was that a single strand could contain a prescription for not just a single cell, but for more cell types with different functions. This is how multicellular organisms were enabled.
Still, the common thing for most of the cells, especially in a multicellular organism, was maintaining the energy production efficiency. Fermentation was no longer allowed to be the sole source of energy; it must have been followed by the TCA cycle in mitochondria where most of the energy was produced. Keeping that energy production workflow also benefited the cells with proper management of waste products. High-energy products of fermentation were utilized in mitochondria for ATP production rather than disturbing normal cell reactions, including inducing mutation in DNA.
In an organism, like a human, there are situations where the energy efficiency mechanisms are suspended.
One such situation is excessive training where energy delivery speed is prioritized above efficiency.
Glycolysis (glucose fermentation) is much faster than the proper cycle of glucose processing involving mitochondria. That is why, when you overexercise a muscle, it will start delivering energy primarily through fermentation of glucose. Its product, lactic acid, will be released into the muscle tissue, causing muscle soreness.
Another circumstance where mitochondria are circumvented is inflammation and reduced oxygen availability.
If the condition is chronic, the mitochondria might be permanently damaged, and the cell reverts to its most primitive program of fermentation and uncontrolled multiplication. This is cancer.
The energy generation in cells is called metabolism. Cells with inactive or damaged mitochondria cannot generate energy in a proper efficient way. This is why, contrary to the contemporary medicine dogma, cancer is primarily a metabolic rather than genetic disease. Genetic mutations found in cancers are a secondary effect caused by highly energetic products of glycolysis interacting with genes.
When a patient suspected of cancer comes to a hospital, contemporary health care procedures would put him through a number of diagnostic tests.
One of the most prominent tests that is done for almost all types of cancer is a PET scan. In that test, the instrument would look for an abnormal glucose uptake by cells. A cancer cell needs over 10 times more glucose molecules than a healthy cell of the same tissue because it relies on fermentation rather than on processes involving mitochondria.
The remarkable thing is that the PET tests are common for almost all types of cancers. Some exceptions are tissues, like prostate, where metabolism is so slow that even excessive glucose uptake is small compared to neighboring tissues and the background gives a stronger signal than the tissue of interest.
Another curiosity is that medicine practitioners are so fixated on genetic origins of cancer that the metabolic side of the disease is utilized in the operating principle of PET tomography that it uses on a daily basis but still underexplored in actual anti-cancer treatments.
Based on ideas presented in this post, a anti-cancer treatment has been devised and successfully applied to a breast cancer patient. See the wygraczrakiem.pl website for details.
