“According to Seyfried, the mutations at the heart of the SMT of cancer were downstream to the true cause: damaged mitochondria. They are a side effect, an epiphenomenon. The upshot is that mutations to DNA ‘arise as effects rather than as causes of tumorigenesis,’ Seyfried said. Mutations seen in the DNA of cancer cells are ‘red herrings’ that sent researchers on a futile hunt.
The most striking evidence that Seyfried dug up was from the late 1980s: a series of uncomplicated experiments that drew remarkable conclusions. Not all experiments are created equal; some are better than others. Experiments that are technically simple in design yet offer results that answer big questions tend to leave a lasting mark in their fields.
Two groups working independently, one in Vermont and the other in Texas, performed a meticulous series of nuclear transfer experiments, both with shocking results. The experiments consisted of a simple transfer. Warren Schaeffer’s group at the University of Vermont wondered how much control the cytoplasm (where all the mitochondria reside) had over the process of tumorigenesis. To find out they conceived of a beautiful experiment. Simply put, they took the nucleus of a cancer cell and transferred it into a healthy cell with its nucleus removed. The reconstituted cell (or recon) now contained the DNA of the cancer cell, with all its supposed driver mutations, but retained the cytoplasm and mitochondria of a noncancerous cell.
The recon now had tremendous power. It alone could answer the question of who was right: Warburg or Varmus and Bishop. If mutations to DNA cause and drove cancer, the recons should be cancerous, regardless of their mitochondria. But, if, as Warburg, Pederson, and Seyfried contended, the mitochondria are responsible for starting and driving cancer and mutations were largely irrelevant, the recons should be normal, healthy cells.”
How’s that for a fascinating experiment?
Imagine a cancerous cell with a cancerous nucleus and a cancerous cytoplasm (where the mitochondria hang out). Now, imagine being able to take the cancerous nucleus out of the cancerous cell and drop it into a healthy cytoplasm—replacing the healthy nucleus with the cancerous one in the “recon” cell.
What do you think science says should happen?
Well, the answer depends on your paradigm. If you ascribe to the somatic mutation theory of cancer, you’d expect the cancerous nucleus to make the cell cancerous. If you’re a metabolic theory of cancer guy or gal, you wouldn’t expect it to make a difference.
As it turns out, when the recon cells were dropped into 68 mice, only one of them grew a tumor. (Which makes no sense if the CAUSE of cancer is damaged DNA.)
But get this.
If you reverse the experiment and take cancerous CYTOPLASM (/mitochondria) and drop that into a recon cell with a healthy nucleus guess what happens?
“When they transplanted the recons containing malignant cytoplasm into newborn mice, 97 percent of the mice developed tumors.”
Again: Less than 2% of the rats got cancer when the nucleus of the recon cell was cancerous. 97% (!!!) got cancer when the nucleus was fine but the cytoplasm of the recon cell was cancerous.
That’s crazy. Guess what happened when the researchers shared their results? Crickets. “Astonishingly, rather than shaking the very foundation of cancer biology, the claim was ignored—even worse than being argued against.”
“Seyfried reflected on the lost importance of the experiments, saying, ‘In summary, the origin of carcinogenesis resides with the mitochondria in the cytoplasm, not with the genome in the nucleus.’”
Over the last several years, even the iconic discoverer of the double helix himself, James Watson, is moving away from the purely genetic theory into an epigenetic approach.
I’m going to skip a detailed accounting of epigenetics (which literally means “above the genes” and represents the environmental and lifestyle factors that influence gene expression) but know this: “Seyfried illuminated basic research showing the important epigenetic signaling that travels from the damaged mitochondria to the nucleus, the missing link to a complete metabolic theory of cancer.”