For the last 100 years or so researchers have been chasing the elusive cure for cancer, yet the World Health Organization reports that 8.8 million people died worldwide in 2015 of the disease, and the National Cancer Institute reported an estimated 1.5 million people will be diagnosed with cancer in the United States in 2016.
No other disease in human history has remained as big a mystery as cancer. Not only do researchers still not know what causes cancer, treatment and increased lifespan has changed little since doctors first started blasting the human body with toxins in the form of chemotherapy. To be sure there has been progress in treating some cancers with a cocktail of chemotherapy, radiation, and pharmaceuticals, but the outlook for most cancer patients remains as grim as ever.
In a world where we can create artificial limbs, send satellites to mars, and map the human genome, why has there been no discovery on the cause of cancer and how to turn it off in the human body? Turns out, we may have spent the last few decades looking in the wrong place and the answer may be more simple than researchers once thought.
When Watson and Crick unlocked the human genome in the 1950s, researchers were excitedly optimistic that the mystery of cancer would soon be discovered. Dollars once designated to other areas of cancer research were diverted into projects that looked at sequencing DNA mutations, and within the span of a few decades, the theory that cancer is precipitated and driven in the human genome was the accepted science in academia and research.
In 2006, the National Cancer Institute together with the National Human Genome Research Institute collaborated to create the Cancer Genome Atlas (TCGA). By this time, the DNA theory of cancer was taught as proven dogma in universities everywhere, and on its own website, TCGA states: “There are at least 200 forms of cancer, and many more subtypes. Each of these is caused by errors in DNA that cause cells to grow uncontrolled. Identifying the changes in each cancer’s complete set of DNA–its genome–and understanding how such changes interact to drive the disease will lay the foundation for improving cancer prevention, early detection and treatment.”
TCGA’s statement clearly demonstrates the staying power of the DNA theory of cancer. Yet, TCGA failed to prove its own theory, and after almost a decade, its herculean effort to genetically profile 10,000 tumors officially ended in 2015. Although the project provided a valuable database on cancer, since its shuttering, the elephant in the room could now be addressed. If DNA mutations do not cause cancer, are we looking in the wrong place?
By admitting that the sequencing of DNA mutations shed no light on the etiology of cancer, a new generation of researchers are now free to step outside of the genome paradigm and take a fresh look at the genesis of cancer—though it will probably take some time before the big money of pharmaceutical investors and biochemical research follows.
And what many curious clinicians are discovering is that an idea that was once old is new again. Otto Warburg, a German researcher and the sole recipient of the Nobel Prize in Physiology, hypothesized as early as the 1930s that cancer was a metabolic, or cellular, disease. Warburg, unarguably one of the twentieth centuries leading biochemist, clung to his theory up to his death in 1970.
Warburg’s theory is simple. His research showed that normal human cells generate energy aerobically, that is through the cell’s respiration mechanism (today known as mitochondria) or they can produce energy anaerobically, or by the fermentation of glucose, a less efficient method of generating energy. What he found was that healthy cells generate most of their energy aerobically, but cancer cells generate most of their energy anaerobically, even when oxygen is present. Warburg summed it up this way:
“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.”
Warburg discovered that, unlike normal cells, cancer cells fermented glucose in the presence of oxygen, which has since come to be called the Warburg Effect. Warburg’s research found that cancer cells didn’t produce any more or any less energy than normal cells, they just did it in a different way. Most striking, he found that without exception this defective method of generating cellular energy was found in all cancerous tumor cells. It was the smoking gun between cancer cells and normal cells even if it wasn’t completely understood at the time. Simply put, the damaged cancer cells were thriving off sugar.
While the majority of academia and research dollars were focused on DNA mapping, there were researches who continued to build on Warburg’s work. Pete Pederson, a biochemist with Johns Hopkins University, and a second generation disciple of Warburg’s work, not only confirmed Warburg’s work that cancer cells were thriving off of sugar via fermentation, he found that there were fewer mitochondria and that those left were damaged. Today, we know that healthy mitochondria is key in the synthesis of creating proteins and communicating with the cell’s nucleus to burn the clean fuel of ketones and fats rather than creating energy through glucose.
Professor Thomas Seyfried, who initially believed that the key to unlocking cancer was in the human genome, was instrumental in compiling previous nuclear transfer study data that, once examined, did much to plant seeds of doubt on his theory of cancer. Seyfried examined experiments that took the nucleus of a cancer cell and put it in a normal cell that had its nucleus removed. This cell was then transplanted into mice. And the mice didn’t get cancer. The biochemist then flipped the study, transplanting the nucleus of a normal cell into a cancer cell and then transplanting them into mice. A whopping 98% of the mice got cancer. Clearly, this was not what he would have expected.
Later in his work with drug therapies, Seyfried noticed in one experiment that mice given a cancer drug were losing their appetites and thus lost weight. The control group of mice were adjusted to keep the test on course, but it still ended in a surprise. The tumor growth in the mice with cancer had slowed down. This observation made Seyfried wonder if other known anticancer drugs might be operating through a restricted caloric diet as well. He began testing other drugs and it turned out that they did. It was the reduced calories that produced the anti-tumor effect—not the drug. This led Seyfried down the path of exploring the metabolics of cells. He wanted to know why a restricted caloric diet was slowing the growth of cancer tumors.
Seyfried was soon able to answer his own question. He found that caloric restriction drives down blood glucose, forcing cancer cells to compete with healthy cells for fuel. By keeping overall calories restricted and eliminating carbohydrates in favor of fats, he was able to show that the diet put metabolic pressure on the cancer cells. Once healthy cells were forced to change their energy generation, they manufactured a molecule called ketone to take the place of glucose as a source of fuel.
Fast forward to researcher Dominic D’Agostiono. As a young scientist, D’Agostino went to work for the Naval Research Laboratory after receiving his PhD. In one of his studies, D’Agostino noted that particular cells appeared vulnerable to the damaging effects of high concentrations of oxygen. The cells were bubbling up and then exploding. When he investigated the origin of the cells, he discovered that they were cells from a stage four cancer patient, which ultimately led him, like Seyfried and others, to Warburg and Pederson’s work.
Today, D’Agostino is an assistant professor in the Department of Molecular Pharmacology and Physiology at the South Florida Morsani College of Medicine and the senior research scientist at the Institute of Human and Machine Cognition. Much of D’Agostino’s work focuses on ketosis, ketones, and the ketogenic diet. D’Agostino proposes that a high-fat, moderate protein, low-carbohydrate ketogenic diet is effective in treating not just cancer, but other diseases as well.
So what exactly are ketones and why has the ketogenic diet proved so effective in treating cancer? Research has shown that in order to shrink or completely eradicate cancer cells, which thrive off blood glucose, you have to starve them of sugar. D’Agostino and others have shown that by depriving the body of glucose via intermittent fasting and a low carbohydrate diet, the body will start producing ketones, a jet fuel of sorts that burns fat and provides energy to healthy cells while starving cancer cells. It also has interesting implications for people who are obese and pre-diabetic.
Refined carbohydrates turn to sugar in the body, which is absorbed by the body’s cells. When the body is inundated with excess glucose, it goes to the liver where it is metabolized as fat. People who suffer with obesity, diabetes, cancer, and inflammatory diseases, all seem to have compromised metabolic systems. It may be a stretch to say that diets high in sugar and refined carbohydrates are directly damaging the body’s mitochondria, but there is something to what these researchers are finding in how the body performs when it is in a ketogenic state.
If you are interested in hearing more about ketones and the ketogenic diet for treating cancer, you can easily search YouTube for lectures given by Seyfried, D’Agostino, and others. If you just want to understand more about the metabolic theory of cancer, I highly recommend Travis Christofferson’s book, Tripping over the Truth, a really good read that ties the history of cancer research into a coherent read for the layperson such as myself. So just put that cupcake down and cut out the pasta. Reign well.