“It’s the metabolism stupid” is a wry nod to President Bill Clinton’s famous 1992 campaign slogan: “The economy, stupid.” As we will see, this phrase is startling in its simplistic defining of the cancer complexity and as an overall reaching principle behind cancer. This phrase is stepping back and looking at the entire forest instead of looking at minute details that could never and will never explain the forest ecosystem.

Otto Warburg started with his famous elucidation of cancer’s ability to metabolize sugar in an extremely inefficient manner even in the presence of oxygen. Then there is a long list of researchers who have blazed a trail for those who can see are easily able to follow. For example, Thomas Seyfried of Boston College has a seminal book, Cancer as a Metabolic Disease, which elucidates the failings of seeing cancer as a genetic cause and the very promising results of seeing cancer as damaged mitochondrial respiration.

Then there is Dominic D’Agostino of the University of Southern Florida and his work with the U.S. Defense Department. He is known for his work with therapeutic ketosis and hyperbaric oxygen for the treatment and management of cancer. He found that normal cells can adapt to the utilization of fats and ketones while cancer cells lack this adaptive ability. Thus cancer cells are sensitive and vulnerable to both metabolic and oxidative therapies that normal cells can easily utilize.

Mina Bissell at the Lawrence Berkeley National Laboratory had a 2012 TED talk where she describes her work with cancer cells. Placing cancer cells in a normal microenvironment could cause the cancer cells to revert to normal thus showing that the microenvironment around the cancer cell is extremely important.

Peter Pedersen and Young Hee Ko at Johns Hopkins have done experiments with metabolic therapies — especially with 3-bromopyruvate, which has cytotoxic effects on cancer cells yet do not damage normal cells and their normal metabolism.

Even such luminaries as James Watson of Watson and Crick Nobel Prize DNA fame has said that looking for cancer metabolism treatments is more promising than a gene-focused approach. Specifically, he has said that looking for the genes that cause cancer has been “remarkably unhelpful” — and this from a dean of DNA research.

Kaipparettu et al 2013 have found that if you switch out a cancer cell’s nucleus for a normal cell’s nucleus there is no change and that the cancer cell remains cancerous. The opposite then is to switch out a normal cell’s nucleus for a cancer cell’s nucleus.

If cancer were genetic then one would think that normal cell would become cancerous. However, the reality is that the normal cell with a cancer nuclei remains a normal cell. So then it is the cytoplasm and not the nucleus that determines the tumorigenicity of a cell. This was elucidated as early as 1948 by Cyril Darlington.