In 1931, Dr. Otto Warburg won the Nobel Prize in Physiology for his discovery that cancer cells have a fundamentally different energy metabolism compared to healthy cells.

Most experts consider him to be the greatest biochemist of the 20th century. His lab staff also included Hans Krebs, Ph. D., after whom the Krebs cycle¹ was named.

The Krebs cycle refers to the oxidative reduction pathways that occur in the mitochondria. So just how does the metabolic inflexibility of cancer cells differ from healthy cells?

A cell can produce energy in two ways: aerobically, in the mitochondria, or anaerobically, in the cytoplasm, the latter of which generates lactic acid — a toxic byproduct. Warburg discovered that in the presence of oxygen, cancer cells overproduce lactic acid. This is known as The Warburg Effect.

Mitochondrial energy production is far more efficient, capable of generating 18 times more energy in the form of adenosine triphosphate (ATP) than anaerobic energy generation.

Warburg concluded that the prime cause of cancer was the reversion of energy production from aerobic energy generation to a more primitive form of energy production, anaerobic fermentation.

To reverse cancer, he believed you had to disrupt the energy production cycle that is feeding the tumor, and that by reverting back to aerobic energy metabolism you could effectively “starve” it into remission.

Although he was never able to conclusively prove it, he maintained this view until his death in 1970. One of his goals in life was to discover the cure for cancer. Sadly, as so typically happens in science, his theories were never accepted by conventional science despite his academic pedigree — until now.

The New York Times² recently published a long, detailed article about the history of modern cancer research, including Warburg’s theories on cancer, which are now becoming more widely accepted.

Sugar Feeds Cancer

Another simpler way of explaining Warburg’s discovery is that cancer cells are primarily fueled by the burning of sugar anaerobically. Without sugar, most cancer cells simply lack the metabolic flexibility to survive. As noted in the New York Times (NYT) featured article:

“[T]he Warburg effect is estimated to occur in up to 80 percent of cancers. [A] positron emission tomography (PET) scan, which has emerged as an important tool in the staging and diagnosis of cancer works simply by revealing the places in the body where cells are consuming extra glucose.

In many cases, the more glucose a tumor consumes, the worse a patient’s prognosis.”

Unfortunately, Warburg’s theories quickly vanished into obscurity once scientists turned their attention toward genetics. Molecular biologists James Watson, Ph. D., and Francis Crick, Ph. D., discovered DNA in 1953 and from that point on, cancer research began to primarily focus on genetics.

The gene hypothesis gained even more momentum once Dr. Harold Varmus and Dr. Michael Bishop won the Nobel Prize in 1976 for finding viral oncogenes within the DNA of cancer cells.

At that point, the attention fell squarely on genetic mutations, and the theory that cancer cells are simply distorted versions of normal cells began to take hold.

The Warburg Revival

It would take another 30 years before the next major revision to the reigning cancer hypothesis. In 2006, the Cancer Genome Atlas project, designed to identify all the mutations thought to be causative for cancer, came to an astonishing conclusion — the genetic mutations are actually far more random than previously suspected.

In fact, they’re so random it’s virtually impossible to pin down the genetic origin of cancer. Some cancerous tumors even have NO mutations at all. Rather than offering the conclusive evidence needed to put an end to cancer, the Cancer Genome Atlas project revealed something was clearly missing from the equation.

With time, researchers began pondering whether cancer development might in fact hinge on Warburg’s theory on energy metabolism. In recent years, scientists have come to realize that it’s not the genetic defects that cause cancer.

Rather mitochondrial damage happens first, which then triggers nuclear genetic mutations. As noted by The New York Times:

“There are typically many mutations in a single cancer. But there are a limited number of ways that the body can produce energy and support rapid growth. Cancer cells rely on these fuels in a way that healthy cells don’t.

The hope of scientists at the forefront of the Warburg revival is that they will be able to slow — or even stop — tumors by disrupting one or more of the many chemical reactions a cell uses to proliferate, and, in the process, starve cancer cells of the nutrients they desperately need to grow.

Even James Watson, Ph.D. one of the fathers of molecular biology, is convinced that targeting metabolism is a more promising avenue in current cancer research than gene-centered approaches …

‘I never thought … I’d ever have to learn the Krebs cycle,’ he said, referring to the reactions … by which a cell powers itself. ‘Now I realize I have to.'”

Cancer-Causing Genes Regulate Cells’ Nutrient Consumption

The genetic component has not completely fallen by the wayside though. Scientists have discovered that a number of genes known to promote cancer by influencing cell division — including a gene called AKT — also regulate cells’ consumption of nutrients. So certain genes do appear to play a role in cancer cells’ overconsumption of sugar.

“Dr. Craig Thompson, the president and chief executive of the Memorial Sloan Kettering Cancer Center, has been among the most outspoken proponents of this renewed focus on metabolism …

His research showed that cells need to receive instructions from other cells to eat, just as they require instructions from other cells to divide.

Thompson hypothesized that if he could identify the mutations that lead a cell to eat more glucose than it should, it would go a long way toward explaining how the Warburg effect and cancer begin,” The New York Times writes.

“The protein created by AKT is part of a chain of signaling proteins that is mutated in up to 80 percent of all cancers. Thompson says that once these proteins go into overdrive, a cell no longer worries about signals from other cells to eat; it instead stuffs itself with glucose.

Thompson discovered he could induce the ‘full Warburg effect’ simply by placing an activated AKT protein into a normal cell. When that happens, Thompson says, the cells begin to do what every single-celled organism will do in the presence of food: eat as much as it can and make as many copies of itself as possible.”

Whereas healthy cells have a feedback mechanism that makes it conserve resources when there’s a lack of food, cancer cells do not have this mechanism, and feed continuously.

As noted by Dr. Chi Van Dang, director of the Abramson Cancer Center at the University of Pennsylvania, cancer cells are “addicted to nutrients,” and “when they can’t consume enough, they begin to die. The addiction to nutrients explains why changes to metabolic pathways are so common and tend to arise first as a cell progresses toward cancer.”