Tuesday, July 08, 2008

Ode Magazine - Cancer's Achilles' Heel

Ode posted this very interesting article about the mechanisms of cancer -- which were discovered back in the 1930s, except that no one took the researcher seriously. That sucks. We lost 80 years or so of possible research because we ignored this one man's strange idea.

Cancer's Achilles' heel

An old, once-abandoned theory about cancer is revived, offering hope for a raft of new non-toxic treatments.

Tony Edwards | June 2008 issue

Medical progress is invariably considered futuristic, but one bit of buzz in the world of cancer research surrounds a man who did most of his work in the 1930s. His name is Otto Warburg, and he’s a German biochemist who—although he was awarded the Nobel Prize for medicine—died in 1970 with his groundbreaking cancer theory discredited and all but forgotten. Today, however, scientists are looking back at his work, acknowledging its importance.

When Warburg proposed his theory about cancer in 1924, the condition was relatively rare, so cancer research was virgin territory. Trained in both physics and chemistry, Warburg studied the assimilation of carbon dioxide and oxygen in plant and animal cells in his late thirties, and noticed something strange about cancer cells. They didn’t use oxygen the same way as normal cells; in fact, they hardly used oxygen at all.

Normal cells take in oxygen through their mitochondria, descendants of bacteria in the original single-celled ancestors of animals and plants. The mitochondria use oxygen to break up carbohydrate molecules (glucose) and release energy. But Warburg discovered cancer cells seem to bypass the mitochondria. Instead, they get energy from a process he called fermentation (now termed “glycolisis”), in which energy is extracted from glucose without the use of oxygen.

To his contemporaries, this was curious, but for Warburg it was fundamental. “The prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar,” he told fellow scientists a few years before he died. Warburg proved his theory by culturing animal cells in a test tube, then growing them under reduced oxygen pressure—within 48 hours they had become cancerous. Even when restored to normal oxygen pressure, the artificially created cancer cells carried on dividing into yet more cancer cells. Once the fermentation process had been established in each cell, said Warburg, the process was “irreversible.”

Fast-forward to 2002 in the department of molecular biology at the University of Madrid. There, a group of scientists was investigating the detailed metabolic processes involved in liver, kidney and colon cancer. Their findings? Two separate mechanisms spurred the cancer’s growth, both with the same result: the inhibition of the mitochondria in normal cells. Warburg had lacked the technology to understand the mechanisms behind his theory, but here was the first vindication of it.

The Spanish scientists were quick to acknowledge that their findings offered “strong support for the Warburg hypothesis.” The team has now discovered similar mechanisms in lung and breast cancers.

Subsequently, a group of molecular biologists at the University of Texas in the U.S. has confirmed that cancer cells thrive in an oxygen-depleted environment and shown for the first time that if glycolisis is inhibited, cancer cells die off at a fierce rate.

Teams at Harvard University and the Massachusetts Institute of Technology in the U.S., led by professor Stuart Schreiber, have since looked in detail at how normal cells change into cancer cells. Focusing on the cells’ metabolism, the teams rediscovered what Warburg proposed 70 years before. As cells become cancerous, they stop getting energy from their mitochondria, progress to glycolisis, no longer take in and release oxygen and wind up oxygen-depleted. What’s more, this process seems to have a genetic component. “We have gained insight into the relationship between two models of carcinogenesis—the Warburg hypothesis and the one based on cancer-causing genes,” Schreiber wrote in a 2005 paper. “Rather than being opposing models, the two are interlinked.”

Warburg’s hypothesis also ties in with a less mainstream theory that connects cancer and acidity. For years, alternative cancer therapists have recommended an alkaline diet to fight cancer. The Warburg Effect provides a possible explanation, since the major by-product of glycolisis is lactic acid. Indeed, recent speculation is that the main way cancer spreads is through the production of lactic acid.

This hunger for glucose was once thought to be a product of tumour growth, but now that research has rediscovered it’s fundamental, the hunt is on to find compounds to block or reverse it. Experts are speculating that cancer’s Achilles’ heel may be its “sweet tooth.”

So are there any existing treatments that exploit the Warburg Effect? In a 1967 article, Warburg himself recommended “always add to food … the active groups of the respiratory enzymes,” his term for micronutrients. Since his death, hundreds of studies have been done on micronutrients and cancer prevention. According to a 2006 clinical review published in Acta Bio Medica, the most valuable micronutrients include selenium, folic acid, vitamin B12, the carotenoids (alpha-carotene, beta-carotene, lycopene, lutein) and vitamin D. Adding calcium to vitamin D can provide extra cancer protection, according to a 2007 study in the American Journal of Clinical Nutrition. Although Warburg didn’t mention it, exercise increases blood oxygenation, and should be of benefit. A 2006 survey shows “compelling evidence” that moderate routine physical activity helps prevent breast and colon cancer.

The most active nutritional research is taking place in Warburg’s native country at the University of Jena. There, a team headed by medical researcher Michael Ristow is researching Warburg’s findings—in particular his pessimistic claim that cancer is irreversible. Ristow’s group has shown the Nobel laureate may have been mistaken. By testing a naturally occurring human protein called frataxin known to stimulate mitochondria, these researchers have shown cancer cells can be “forced into mitochondrial metabolism.” This suppresses cancer growth, says Ristow, whose ultimate hope is to find completely nutritional cancer treatments.

Warburg would, no doubt, approve.

This article is excerpted from the September 2007 issue of the British medical newsletter What Doctors Don’t Tell You. Find out more: wddty.co.uk.

No comments: