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What If Cancer Is a Metabolic Disease—Not a Genetic One?

The numbers don’t lie. This year, almost six hundred thousand Americans will die from cancer.

One in two men and one in three women will be diagnosed in their lifetimes. Despite embellished announcements from government actuaries, the real death rates from cancer are the same today as they were in the 1950s. We can’t seem to penetrate its elusive armor, and it’s not for lack of trying. Cancer receives more funding from the National Institute of Health (NIH) than any other disease. Not to mention that it is under investigation at every major pharmaceutical company around the world.

Why, in a century of breathtaking progress has progress in treating cancer remained so static? Radiation, still one of the main methods of treatment, was invented well over one hundred years ago, when horses and buggies still occupied the streets.

There is no shortage of explanations for the stagnant progress. Some suggest that, because of the collective failure of academia, government, and industry, a culture has developed that discourages risk-taking and encourages narrow thinking. Some say it is due to not enough funding. Others believe that it is a manifestation of the complexity of the disease itself. Cancer is just that difficult.

Travis Christofferson, author of the groundbreaking book Tripping Over the Truth, says he’s looked for the answer to this question in a place others haven’t—one protected by an invisible dome of dogma, large-scale group think, and institutional inertia. Maybe the reason for the stunted progress goes far deeper than we thought, he suggests. Maybe it is fundamental, going all the way to the scientific bedrock at the true heart of the disease. To utter it is heretical, to say it out loud invites scoffs, dismissal, even outright anger, but here’s what Christofferson thinks is the problem: Maybe we’ve mischaracterized the origin of cancer. Maybe cancer is not a genetic disease after all. Maybe we are losing the war against cancer because scientists are chasing a flawed scientific paradigm, and cancer is not a disease of damaged DNA but rather one of defective metabolism.

This idea didn’t start with Christofferson. “I stumbled onto it a few years ago in a book called Cancer as a Metabolic Disease,” he says. It’s author, Thomas Seyfried, PhD, of Boston College, is bold, confident, outspoken, and very smart. But the original claim came from a remarkable German scientist named Otto Warburg in 1924. Throughout most of the subsequent century Warburg’s claim was only a side note in reviews on the subject of cancer. It never really gained a critical mass of supporters. It remained just a curious observation. By the 1960s, his theory had all but faded into oblivion. When Warburg died in 1970, his antiquated hypothesis could have died with him. It would have slipped into oblivion if Peter Pedersen, PhD of Johns Hopkins University School of Medicine hadn’t noticed it and methodically coaxed it back to life. In the 1970s and the 1980s, he was alone in his belief that Warburg was right.

Warburg’s observation was this: Cancer cells have a perverted method of generating energy. They truncate the conversion of glucose (sugar) into energy. They depend much less on the efficient process of aerobic respiration, using oxygen to produce energy—instead relying much more on the ancient and highly inefficient pathway known as fermentation. Later in his career, Warburg contended that this was the true origin of cancer. The cell’s ability to generate energy through the oxidative pathway is damaged, and the cell reverts to fermentation. He said, “Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.

In 2012, Seyfried expanded upon Warburg’s hypothesis (and Pederson’s work), noting that, across the board, cancer cells have damaged cellular organelles called mitochondria. Typically each animal cell, including those of humans, has one thousand to two thousand mitochondria. Mitochondria are thought of as the cellular power plants. They generate energy through oxidative respiration, supplying the body with the energy it needs to function. The damaged mitochondria, unable to generate enough energy for cellular survival, then send out emergency signals to the nucleus, pleading for it to switch on emergency generators. Once this call is made and DNA responds, the entire complexion of the cell changes. It begins to exhibit the hallmark features of cancer: uncontrollable proliferation, genomic instability (the increased probability that DNA mutation will occur), evasion of cell death, and so forth.

The process is probably a primordial survival mechanism designed to nurture cells through the transient moments when little oxygen was available that undoubtedly occurred as the planet’s first cells evolved toward increasing complexity. A vestige of our evolutionary past. The bottom line is this: Damage to the mitochondria happens first, then genomic instability, and then mutations of DNA. The upshot, according to Seyfried, is that the mutations to DNA, thought to precipitate a drive the disease, are really only a side effect and have sent researchers on a multidecade, multibillion-dollar wild-goose chase. It is a bold proclamation, and the majority of cancer researchers disagree with Seyfried’s assertions, but history is replete with examples of humanity getting big issues wrong for extended periods of time.

Was Warburg right? It may be too early to say. The therapeutic implications of the metabolic theory are that every type of cancer is treatable. Although largely unknown and underappreciated, therapies devised from this theory have shown remarkable results. A dietary protocol developed by Seyfried has shown promise in slowing the growth of cancer and working synergistically with existing therapies while mitigating side effects. Although unquestionably in their infancy, metabolic therapies have demonstrated incredible promise. Without question, they merit more attention.

Want the full scientific and human story about the revival of Warburg’s theory and the profound therapeutical implications that come with it? Don’t miss Christofferson’s Tripping Over the Truth: How the Metabolic Theory of Cancer Is Overturning One of Medicine’s Most Entrenched Paradigms (this article is adapted from the book).


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