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Replies to post #158842 on Anavex Life Sciences Corp (AVXL)
07/22/18 3:47 AM
Is Cancer a Mitochondrial Disease?
Posted on October 1, 2017
“Cancer is a genetic disease. Its primary cause is mutagens in the environment, abetted by time and bad luck. A cell is controlled by the chromosomes in its nucleus, and when just the wrong combination of mutations happens to occur, a cell can begin to grow and multiply uncontrollably. The next crucial step occurs when the cell acquires the ability to travel through the bloodstream and implant somewhere else. The whole pathway from errant cell to malignant cell proceeds via chance mutations. From inception to metastasis, cancer is driven by genetics.”
This theory of cancer is more than 100 years old, but it didn’t become the dominant view until the 1950s, when, after Watson and Crick, genes assumed an exalted position in the study of biology. The “somatic mutation theory” continues to dictate the course of cancer research and treatment today.
It is uncontested that cancer cells have abnormal chromosomes. Dozens of different mutations have been found in malignant cells. They have been catalogued as different oncogenes, and because they are so different in their functions, cancer has been re-conceived from a single disease to a category containing many different diseases with similar symptoms.
Are mutated genes the root cause of cancer? Toxins that commonly break DNA (teratogens) are also found to cause cancer (carcinogens). Radiation, ditto. “Ionizing” radiation packs enough wallop in each photon to break a chemical bond, and is associated with cancer, while non-ionizing radiation (visible, infrared, and radio waves) is not mutagenic and generally not carcinogenic*. This has been taken as powerful circumstantial evidence for the prevailing theory.
A direct answer to the question of whether cancer originates in the nuclear DNA is available from an experiment that is simple in principle: Swap nuclei between two cells, one normal and one malignant. Take the mutated DNA out of a cancer cell and put it in a normal cell, to see if it becomes malignant. Take the un-mutated DNA out of a normal cell and put it in a cancer cell to see if the cell is rescued and restored to health.
This experiment has been technically feasible for more than 30 years, and indeed Barbara Israel and Warren Schaeffer actually performed both experiments at UVM and wrote them up in 1987 [ref, ref]. The results were exactly the opposite of what was expected: The cell with normal cytoplasm and cancerous nucleus was normal; the cell with normal nucleus and cancerous cytoplasm was cancerous. This result has been confirmed in other labs [reviewed by Seyfried, 2015]. Still, the genetic paradigm has a stubborn grip on cancer research and treatment to this day.
An alternative theory of cancer as a metabolic disease was put forth by the Nobel polymath Otto Warburg in the 1930s. The principal proponent of this theory today is Thomas Seyfried of Boston College. Seyfried cites evidence that damage to the nuclear DNA, conventionally thought to be a root cause of cancer, is actually an effect of the damaged mitochondria and irregular metabolism. “The metabolic waste products of fermentation can destabilize the morphogenetic field of the tumor microenvironment thus contributing to inflammation, angiogenesis and progression.”
Respiration and Fermentation
Every cell in our bodies (and almost every cell in all eukaryotes everywhere) makes uses of energy in the form of ATP, adenosine triphosphate. ATP is manufactured in the mitochondria, usually by a controlled burning of sugar to form CO2 and H2O. Highly energy-intensive cells such as muscles and nerves have thousands of mitochondria in each cell. The word “respiration” in this context is used to mean burning sugar in an efficient energy conversion process, yielding 38 ATPs for every sugar molecule. But when oxygen is scarce, perhaps because you’re breathing as fast as you can or sprinting in deep anaerobic mode, another process can be used to rapidly convert available sugar stock to lactic acid, requiring no oxygen at all, but yielding only 2 ATPs per sugar molecule. The latter process is called “fermentation”. (This observation explains the extraordinary effectiveness of interval training (sprints) for weight loss.)
Warburg was among the first to notice [1931] that most cancer cells use fermentation rather than respiration as an energy source. Metabolic studies pointed to damaged mitochondria in tumor cells that had become inefficient in producing sufficient energy through respiration. He theorized that impaired mitochondrial function is the root cause of cancer. In fact, Warburg did some of the early work establishing the role of mitochondria as cellular energy factories.
So most cancer cells are sugar addicts. They consume enormous amounts of sugar, both because they are actively growing and dividing, and also because they use sugar so much less efficiently than normal cells. A PET scan can be used to visualize concentrations of sugar in the body, and PET technology is often used to locate tumors.
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