The Cancer-Preventive Diet

 

 

 

 

The Cancer-Preventive Diet

Dr. Li believes the answer to cancer is to prevent angiogenesis, which can effectively starve any microscopic cancerous growths, preventing them from growing and becoming dangerous.

But how do you prevent angiogenesis, aside from using a drug?

As it turns out, "mother nature has laced a large number of foods, beverages and herbs with naturally occurring inhibitors of angiogenesis," says Li.

So by consuming these anti-angiogenetic foods you can naturally boost your body's defense system and prevent blood vessels from forming and feeding the microscopic tumors that exist in your body at any given time.

As shown on a graph in the video, diet accounts for at least 30-35 percent of all environmentally caused cancers.

So, "eating to starve cancer" could have a dramatic impact on cancer rates across the world.

According to Li, resveratrol from red grapes, for example, have been shown to inhibit abnormal angiogenesis by 60 percent. Even more potent is the ellagic acid found in strawberries.

Other anti-angiogenetic foods include:

Green tea

Berries: strawberries, blackberries, raspberries, blueberries

Cherries

Red grapes

Kale

Turmeric

Nutmeg

Artichokes

Parsley

Garlic

Tomato

Maitake mushroom

 

Logically, different foods contain different potencies of anti-angiogenetic compounds. But interestingly, when researchers evaluated a combination of two of the LEAST potent teas, for example, they discovered that this combination tea had greater potency than any given tea by itself.

"There's synergy," Li states, which should come as no surprise to those of you who are well-versed in holistic nutrition.

Synergy is indeed what makes fresh, whole foods so potently nutritious! The sum is far greater than the individual parts, and this is why it's far more important to focus on eating a diet of whole, organic foods, rather than obsessing about individual nutrients.

 

The Cancer Alternative Foundation Site:

 

The Cancer Alternative Foundation Site

The Cancer Alternative Foundation - 

http://www.thecanceralternative.org/resources

 

The Cancer Alternative Foundation

 

Why An Alkaline Approach Can Successfully Treat Cancer

 

 

http://www.greenmedinfo.com/blog/why-alkaline-approach-can-successfully-treat-cancer

Why An Alkaline Approach Can Successfully Treat Cancer

Posted on: 

Thursday, August 8th 2013 at 2:45 pm

Written By: 

Nancy Elizabeth Shaw

This article is copyrighted by GreenMedInfo LLC, 2013
Visit our Re-post guidelines

Nancy is the founder of The Cancer Alternative Foundation - 

http://www.thecanceralternative.org/resources

In the 1930's, an interesting natural cancer treatment was proposed as a simple, effective answer to cancer – almost any cancer.  This treatment approach is not well known because it is considered alternative or experimental - or even dangerous[i] - by the medical and scientific community and hence has been referenced primarily in obscure publications outside the mainstream press.

This treatment approach is called alkaline therapy or pH therapy, and is based in part on observations of cultures without significant incidence of cancer[ii] and in part on scientific observations of and experimentation with cellular metabolism.[iii]

The principles of pH therapy are very simple.  The metabolism of cancer cells has a very narrow pH tolerance for cellular proliferation (mitosis), which is between 6.5 and 7.5.  As such, if you can interfere with cancer cell metabolism by either lowering or raising the internal cancer cell pH, you can theoretically stop cancer progression.[iv]  

While lowering cancer cell pH (increasing acidity) is effective against cancer cell mitosis in the lab, increasing acid levels in the live body of a cancer patient puts stress on normal cells and causes a lot of pain.  So the proposed alkaline therapy for people is a "high pH therapy" and has been developed to normalize the intracellular pH of the cancer patient's body through elimination of latent acidosis, while increasing the pH of cancer cells to a range above 7.5.  According to published research, it is at that pH they revert to a normal cellular apoptosis cycle (programed cell death).[v]

Ideally, this approach begins with an alkaline diet.  There is general agreement amongst natural healers and medical professionals alike, that changing a cancer patient's diet is extremely helpful when someone is confronted with a cancer diagnosis.  In a previous article, I outlined the six steps that every cancer patient should take to provide the best chance to heal from and prevent future recurrences of cancer using alkaline diet principles.[vi]

The alkaline diet, which is primarily plant-based and avoids sugar, dairy, wheat and other high-gluten grains as well as an excess consumption of fruits, while emphasizing fresh vegetables and vegetable juices along with cruciferous vegetables and greens, changes the body's intracellular pH to come close to the ideal blood pH of 7.3/7.41  - a key metabolic accomplishment on the path to longevity whether you have cancer or not!  An alkaline diet based on vegetables and fruits creates a less-than-optimal environment for cancer proliferation, while at the same time strengthens the immune function and supports healthy cells in the body through improved nutrition.

The second step is to use some nutritional mechanism to move the internal cancer cell pH from the optimal mitosis range of pH 6.5 to 7.5, to above 8, which shortens the life of the cancer cell.  As described by its proponents, alkaline therapy neutralizes the acid waste of the cancer which causes so much pain, interferes with the anaerobic fermentation of glucose that starts the self-feeding acidic cancer wasting cycle called cachexia and in time, can induce remission.  If this theory of alkaline therapy holds true, it should be possible to address cancer without chemotherapy, radiation or surgery and use alkaline therapy as a primary cancer treatment.

This bold statement comes from a somewhat abstruse body of research.  In the 1880's, Louis Pasteur published his work on cellular aerobic respiration and glycolysis.  In 1931, Otto Warburg won the Nobel Prize for his work on the metabolism of tumors and the respiration of cells, which was later summarized in his 1956 paper, On the Origin of Cancer Cells.  His work on cancer expanded upon Pasteur's findings and described respiratory insufficiency and a cellular metabolism of glucose fermentation as the primary trigger for cancer progression[vii].

Warburg's conclusions on cancer were much discussed in scientific circles, as they are academically elegant, but were not accepted by most members of the scientific community engaged in cancer research.  Most cancer researchers in the late 1950's believed that the anaerobic metabolism of cancer cells and their accompanying output of lactic acid was a side effect or an adjunct effect of cancer, not a cause.  Cancer research since the 1960's has focused primarily on genetic aberrations as causative for cancer, and has ignored the body of research on cancer pH and its implications for therapeutic approaches.[viii]

Warburg's work was a catalyst for yet another research effort on the nature of cancer cells, beginning in the 1930's.  A. Keith Brewer, PhD (physicist) performed experiments on the relationship between energized, oxygenated cell membrane and elemental uptake, vs. cellular membranes in an unenergized state such as cancer cells exhibit.  He wrote a number of papers discussing the cellular mechanisms of cancer cells and the changes in metabolism induced or indicated by the lack of or presence of oxygen in combination with other elements, particularly potassium and calcium.   He noted that cancer cells share one characteristic no matter what type of cancer:  they have lost their pH control mechanism.

Brewer's summary conclusion regarding cancer was that by changing the pH of cancer cells to alkaline (above 7.5), they will cease to function as they need an acidic, anaerobic environment to thrive.  In other words, he proposed that cancer cells will die if they can be pushed into an alkaline, oxygenated state.[ix]

Brewer's work cites areas in the world where cancer incidents are very low.  These areas contain concentrations of alkalizing minerals in the soil and water, which are greater than in other parts of the world.  For example, the Hunza of northern Pakistan and the Hopi Indians of the American West share both similar soil and water conditions and diet.  The alkaline elemental minerals of cesium chloride, germanium and rubidium are heavily present in the soil and water.  Ingestion of these elements is correspondingly high.  These peoples also live in similar high, dry climates and grow apricot orchards, traditionally eating the fresh or dried fruit and the seeds each day. 

It should be noted that apricot seeds are the source of the controversial cancer treatment Laetrile or B-17/Amygdalin.[x]   Apricot seeds contain trace amounts of cyanide, which has long been identified as a potential chemotherapeutic agent against cancer proliferation.[xi]   Other similarities in the diet include a low consumption of dairy products, meat and wheat, as these foodstuffs are difficult to farm in high, arid climates and a correspondingly greater consumption of millet, buckwheat, nuts, dried fruits and berries in their traditional diets, all of which contain a similar enhanced (though sill minute) concentration of cyanide.

This is all very interesting, but what does it really mean for cancer patients who wish to avoid the pain of cancer and the typical course of treatment using surgery, chemotherapy and radiation?  What are the conditions that will force cancer cells to change their pH?

Conventional chemotherapeutic agents such as Cytoxan usually cause more damage to normal cells than to cancer cells, because cancer cells have a very thick, unenergized cellular membrane that essentially protects them from absorbing many drugs.  Normal cells have no such protection. 

Conversely, cancer cells have no way to normalize their internal pH, where normal cells are relatively unaffected by high concentrations of alkalizing minerals.  However cancer cells take up primarily two elements:  glucose and potassium.

In practical application, then, it is necessary to find a way to guide alkalizing elements - such as cesium, germanium or rubidium - into cancer cells, without impacting normal cells.  It turns out this can be done using a transport agent that penetrates the bone/blood barriers, then relying on the normal uptake of alkalizing elements that follow the potassium pathway.  Cancer cells appear to have preferential uptake of cesium chloride in particular, but also take up germanium, rubidium, selenium, etc. all through the potassium pathway.

There is a compound that is frequently applied to the skin by arthritis sufferers for relief of inflammation, used in brain surgery to relieve intracranial pressure and topically used in sports medicine and veterinary medicine,[xii] also for reducing inflammation.  This compound is called DMSO and it is formed in the slurry created from soaking wood chips in water that is a bi-product of the paper making industry. 

Folklore has it that workers in the paper making industry were observed to have their hands in water continuously, but they never developed arthritis and had rapidly healing skin and strong nails.  Experimentation with DMSO as a medical treatment began in the 1800's and continues to the present day.  DMSO is medically approved in the United States only for the treatment of interstitial cystitis, a type of inflammation of the bladder.[xiii]

The reason DMSO is so interesting to cancer patients is that, in addition to its anti-inflammatory properties, it is a "carrier agent."  It penetrates the brain/blood barrier and carries with it whatever drug or mineral is mixed with.

There is now some interest in the cancer industry in potentially using DMSO to carry chemotherapeutic agents into cancer cells and get beyond their protective membrane.  However, for the purposes of changing the alkalinity of cancer cells using cesium chloride, germanium, rubidium and other alkalizing minerals, DMSO and its ingestible form, MSM, are an effective medium.  Essentially these agents carry the minerals into all areas of the body including the brain, organs and bone marrow, where they can be used with other nutrients in ordinary cellular metabolism.

Using topically applied and ingested alkaline minerals to change cancer cell pH is not a new idea.  Controlled experiments and the personal use of this method have been ongoing since the mid-1900s.   However, it is important to note that the only FDA approved clinical trial did not have outstanding results.[xiv]  About 50% of the participants died – though if you read the study results in detail you will discover that they had been pronounced terminal before the trial began and some of them never even took one treatment.  Others had side effects ranging from leg cramps to heart arrhythmia.  A careful read will lead you to believe that perhaps they were given too strong a dose in too short a period of time.[xv]

From this research and subsequent studies, it is now understood that alkaline minerals look to normal cells and to cancer cells like potassium.  All cells require potassium to function.  The reason cancer cells take up these alkaline minerals is their resemblance to potassium. 

Functionally, however, these minerals cannot take the place of potassium in cellular metabolism.  While substituting alkaline minerals for potassium creates exactly the desired result in cancer cells – increased alkalinity - when normal cells replace potassium with other minerals over the long term the consequences can be quite serious as it causes electrolyte imbalance, manifested as heart arrhythmia and leg cramps.[xvi]

The remedy to this condition of electrolyte imbalance, caused by replacement of potassium in healthy cells with other alkaline minerals during pH therapy, is simple in practical application.  Alkaline minerals are ingested or applied to the skin only during the day.  Then before sleep, the user must take potassium chloride supplementation along with other electrolytes such as magnesium and calcium if needed.  Monitoring of potassium blood levels every two weeks by a doctor is critical if a cancer patient decides to incorporate alkaline therapy into their cancer regime.   

When properly balanced, the side effects of using alkaline minerals are greatly if not completely remediated by electrolyte rebalancing.  Despite the "fear, fire, foe" tone of Mssrs. Wiens et al in the article cited above[xvii] there is no risk of dying of a heart attack (or leg cramp), unless the patient ignores the proper method using alkaline minerals and is not working in consultation with an experienced specialist.  A caution: electrolyte rebalancing cannot be properly implemented by casual methods such as drinking sports drinks, particularly since commercial products are generally full of sugar and artificial substances.  Electrolyte rebalancing must be carefully applied using specific doses of supplements, based on your personal blood composition, in consultation with a nutrition expert or endocrinologist.

My personal experience with pH therapy has been nothing short of spectacular.  I have seen stage four, terminal cancer patients recover using alkalizing minerals.  There are patients who report untreatable cancers, such as nasal or fully metastasized breast cancers, which after a very persistent course of tiny doses over several years, eventually disappeared altogether.  Patients who have never had chemotherapy or radiation often experience rapid remission after changing to an alkaline diet and incorporating the use of alkaline minerals into their regime. 

However pH therapy using alkaline minerals requires quite a bit of knowledge (do your homework!) and is greatly enhanced with the support of a mineral provider or cancer coach who has the experience to guide you through the process.  Many mineral providers sell minerals, but do not have the ability to assist the users.  Therefore, it is critical to seek a mineral provider who can provide references to extensive information and is available to help you work through the rough spots – and there will be some!

It is my direct personal experience that cancer can be controlled using alkaline minerals.  There are thousands of people who have had similar positive experiences.  Does it work for everyone?  No.  However if high pH therapy is properly applied, it works for a very respectable percentage of cancer sufferers – estimated at upwards of an 80% response rate by providers.  Significant when compared to traditional therapies.

This finding is why I started The Cancer Alternative Foundation - to help cancer patients feel comfortable using effective, natural therapies like pH therapy as part of their overall treatment strategy.  The Foundation simply researches and vets the claims of various alternative offerings for cancer – and there are more than 400!  To date, we have concluded that high pH therapy is one of the most effective alternatives, particularly for later stage cancers.

However alkaline therapy outcomes (as well as those for other sound alternatives) have yet to be documented in a systematic way, such that the medical community could reliably understand the positive impact that incorporating it into cancer treatment could make to hundreds of thousands of cancer sufferers.   Collecting outcomes is a current project at The Cancer Alternative Foundation and should prove invaluable to cancer patients and their doctors and care givers alike.[xviii]

If nothing else, it is my contention that alkaline therapy could be used in a supporting role to conventional treatment, which will only improve the long-term outcome for patients.  It is my hope that this promising and effective natural approach to cancer becomes more accepted by mainstream cancer care providers - as well as those enlightened individuals seeking a natural alternative, who are willing to close their eyes and jump. 

An alkaline approach to cancer can only help them to enjoy their future – as in having one!

Nancy Elizabeth Shaw is a strategist, meta-analyst and Founder of The Cancer Alternative Foundation.  Contact information: www.thecanceralternative.org/contact_us


[i] Cassileth, Barrie R. et al, Herb-Drug Interaction in Oncology, pp. 158-159; Memorial Sloan-Kettering Cancer Center, People's Medical Publishing House, Shelton, CT  2010

[ii] Clark, J., Hunza in the Himalayas, National Geographic, 72, 38-45; 1963

[iii] Brewer, A. Keith and Passwater, R.   Physics of the Cell Membrane V. Mechanisms involved in cancer; American Lab, 1975,-
8, 37-45

[iv] Brewer, A. Keith PhD, Cancer, Its Nature and a Proposed Treatment, 1997; Brewer Science Library; http://www.mwt.net/~drbrewer/brew_art.htm

[v] Ibid, p. 15.

[vi] http://www.greenmedinfo.com/blog/nutrition-information-every-cancer-patient-should-know

[vii] Warburg, Otto, On the Origin of Cancer Cells, Science, February 1956, Vol. 123, No. 3191

[viii] Witting, Rainer and Coy, Johannes, The Role of Glucose Metabolism and Glucose-Associated Signaling in Cancer; Perspectives in Medicinal Chemistry, 2007; 1:64-82. Pp. 2; cited PubMed, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754915

[ix] Cancer: The Mechanism Involved and a High pH Therapy, 1978 papers of A. Keith Brewer, Ph.D. & co-authors, Copyright A. Keith Brewer Foundation, 325 N. Central Ave., Richland Center, Wis, 53581.

[x] Griffin, G. Edward, World Without Cancer:  The Story of Vitamin B17, American Media, Westlake, CA 1974

[xi] Fatma Akinci Yildirim and M. Atilla Askin: Variability of amygdalin content in seeds of sweet and bitter apricot cultivars in Turkey. African Journal of Biotechnology Vol. 9(39), pp. 6522-6524, 27 September, 2010; Available online at http://www.academicjournals.org/AJB; DOI: 10.5897/AJB10.884; 600 mg. of bitter apricot seeds contain up to 1.8 mg of cyanide, where the sweet kernels contain up to .9 mg. of cyanide.

[xii]http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074679.htm.

[xiii]http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/dmso; When used for this condition, a 50% solution of DMSO is instilled into the bladder through a catheter and left there for about 15 minutes to relieve the inflammation

[xiv]http://www.ncbi.nlm.nih.gov/pubmed/6522427

[xv] http://www.ncbi.nlm.nih.gov/pubmed/19746253

[xvi] Weins, Matthew et al; Cesium chloride-induced torsades de pointes, Can J Cardiol. 2009 September; 25(9): e329–e331; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780897

[xvii] Ibid.

[xviii] To donate to The Cancer Alternative Foundation's Alternative Outcomes Database, see the website:  http://www.thecanceralternative.org/donate_to_the_cancer_alternative_foundation

 

 

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

 

http://www.greenmedinfo.com/blog/why-alkaline-approach-can-successfully-treat-cancer

 

Starve Cancer to Death - Warburg effect

 

https://www.nytimes.com/2016/05/15/magazine/warburg-effect-an-old-idea-revived-starve-cancer-to-death.html

 

CreditPhoto illustration by Cristiana Couceiro. Source photograph from Getty Images and Wikimedia Commons.

An Old Idea, Revived:
Starve Cancer to Death

In the early 20th century, the German biochemist Otto Warburg
believed that tumors could be treated by disrupting their source
of energy. His idea was dismissed for decades — until now.

By SAM APPLEMAY 12, 2016

The story of modern cancer research begins, somewhat improbably, with the sea urchin. In the first decade of the 20th century, the German biologist Theodor Boveri discovered that if he fertilized sea-urchin eggs with two sperm rather than one, some of the cells would end up with the wrong number of chromosomes and fail to develop properly. It was the era before modern genetics, but Boveri was aware that cancer cells, like the deformed sea urchin cells, had abnormal chromosomes; whatever caused cancer, he surmised, had something to do with chromosomes.

Today Boveri is celebrated for discovering the origins of cancer, but another German scientist, Otto Warburg, was studying sea-urchin eggs around the same time as Boveri. His research, too, was hailed as a major breakthrough in our understanding of cancer. But in the following decades, Warburg’s discovery would largely disappear from the cancer narrative, his contributions considered so negligible that they were left out of textbooks altogether.

Unlike Boveri, Warburg wasn’t interested in the chromosomes of sea-urchin eggs. Rather, Warburg was focused on energy, specifically on how the eggs fueled their growth. By the time Warburg turned his attention from sea-urchin cells to the cells of a rat tumor, in 1923, he knew that sea-urchin eggs increased their oxygen consumption significantly as they grew, so he expected to see a similar need for extra oxygen in the rat tumor. Instead, the cancer cells fueled their growth by swallowing up enormous amounts of glucose (blood sugar) and breaking it down without oxygen. The result made no sense. Oxygen-fueled reactions are a much more efficient way of turning food into energy, and there was plenty of oxygen available for the cancer cells to use. But when Warburg tested additional tumors, including ones from humans, he saw the same effect every time. The cancer cells were ravenous for glucose.

Warburg’s discovery, later named the Warburg effect, is estimated to occur in up to 80 percent of cancers. It is so fundamental to most cancers that 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.

In the years following his breakthrough, Warburg became convinced that the Warburg effect occurs because cells are unable to use oxygen properly and that this damaged respiration is, in effect, the starting point of cancer. Well into the 1950s, this theory — which Warburg believed in until his death in 1970 but never proved — remained an important subject of debate within the field. And then, more quickly than anyone could have anticipated, the debate ended. In 1953, James Watson and Francis Crick pieced together the structure of the DNA molecule and set the stage for the triumph of molecular biology’s gene-centered approach to cancer. In the following decades, scientists came to regard cancer as a disease governed by mutated genes, which drive cells into a state of relentless division and proliferation. The metabolic catalysts that Warburg spent his career analyzing began to be referred to as “housekeeping enzymes” — necessary to keep a cell going but largely irrelevant to the deeper story of cancer.

“It was a stampede,” says Thomas Seyfried, a biologist at Boston College, of the move to molecular biology. “Warburg was dropped like a hot potato.” There was every reason to think that Warburg would remain at best a footnote in the history of cancer research. (As Dominic D’Agostino, an associate professor at the University of South Florida Morsani College of Medicine, told me, “The book that my students have to use for their cancer biology course has no mention of cancer metabolism.”) But over the past decade, and the past five years in particular, something unexpected happened: Those housekeeping enzymes have again become one of the most promising areas of cancer research. Scientists now wonder if metabolism could prove to be the long-sought “Achilles’ heel” of cancer, a common weak point in a disease that manifests itself in so many different forms.

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, 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. At his office at the Cold Spring Harbor Laboratory in Long Island, Watson, 88, sat beneath one of the original sketches of the DNA molecule and told me that locating the genes that cause cancer has been “remarkably unhelpful” — the belief that sequencing your DNA is going to extend your life “a cruel illusion.” If he were going into cancer research today, Watson said, he would study biochemistry rather than molecular biology.

“I never thought, until about two months ago, I’d ever have to learn the Krebs cycle,” he said, referring to the reactions, familiar to most high-school biology students, by which a cell powers itself. “Now I realize I have to.”

Born in 1883 into the illustrious Warburg family, Otto Warburg was raised to be a science prodigy. His father, Emil, was one of Germany’s leading physicists, and many of the world’s greatest physicists and chemists, including Albert Einstein and Max Planck, were friends of the family. (When Warburg enlisted in the military during World War I, Einstein sent him a letter urging him to come home for the sake of science.) Those men had explained the mysteries of the universe with a handful of fundamental laws, and the young Warburg came to believe he could bring that same elegant simplicity and clarity to the workings of life. Long before his death, Warburg was considered perhaps the greatest biochemist of the 20th century, a man whose research was vital to our understanding not only of cancer but also of respiration and photosynthesis. In 1931 he won the Nobel Prize for his work on respiration, and he was considered for the award on two other occasions — each time for a different discovery. Records indicate that he would have won in 1944, had the Nazis not forbidden the acceptance of the Nobel by German citizens.

That Warburg was able to live in Germany and continue his research throughout World War II, despite having Jewish ancestry and most likely being gay, speaks to the German obsession with cancer in the first half of the 20th century. At the time, cancer was more prevalent in Germany than in almost any other nation. According to the Stanford historian Robert Proctor, by the 1920s Germany’s escalating cancer rates had become a “major scandal.” A number of top Nazis, including Hitler, are believed to have harbored a particular dread of the disease; Hitler and Joseph Goebbels took the time to discuss new advances in cancer research in the hours leading up to the Nazi invasion of the Soviet Union. Whether Hitler was personally aware of Warburg’s research is unknown, but one of Warburg’s former colleagues wrote that several sources told him that “Hitler’s entourage” became convinced that “Warburg was the only scientist who offered a serious hope of producing a cure for cancer one day.”

Although many Jewish scientists fled Germany during the 1930s, Warburg chose to remain. According to his biographer, the Nobel Prize-winning biochemist Hans Krebs, who worked in Warburg’s lab, “science was the dominant emotion” of Warburg’s adult life, “virtually subjugating all other emotions.” In Krebs’s telling, Warburg spent years building a small team of specially trained technicians who knew how to run his experiments, and he feared that his mission to defeat cancer would be set back significantly if he had to start over. But after the war, Warburg fired all the technicians, suspecting that they had reported his criticisms of the Third Reich to the Gestapo. Warburg’s reckless decision to stay in Nazi Germany most likely came down to his astonishing ego. (Upon learning he had won the Nobel Prize, Warburg’s response was, “It’s high time.”)

“Modesty was not a virtue of Otto Warburg,” says George Klein, a 90-year-old cancer researcher at the Karolinska Institute in Sweden. As a young man, Klein was asked to send cancer cells to Warburg’s lab. A number of years later, Klein’s boss approached Warburg for a recommendation on Klein’s behalf. “George Klein has made a very important contribution to cancer research,” Warburg wrote. “He has sent me the cells with which I have solved the cancer problem.” Klein also recalls the lecture Warburg gave in Stockholm in 1950 at the 50th anniversary of the Nobel Prize. Warburg drew four diagrams on a blackboard explaining the Warburg effect, and then told the members of the audience that they represented all that they needed to know about the biochemistry of cancer.

Warburg was so monumentally stubborn that he refused to use the word “mitochondria,” even after it had been widely accepted as the name for the tiny structures that power cells. Instead Warburg persisted in calling them “grana,” the term he came up with when he identified those structures as the site of cellular respiration. Few things would have been more upsetting to him than the thought of Nazi thugs chasing him out of the beautiful Berlin institute, modeled after a country manor and built specifically for him. After the war, the Russians approached Warburg and offered to erect a new institute in Moscow. Klein recalls that Warburg told them with great pride that both Hitler and Stalin had failed to move him. As Warburg explained to his sister: “Ich war vor Hitler da” — “I was here before Hitler.”

Imagine two engines, the one being driven by complete and the other by incomplete combustion of coal,” Warburg wrote in 1956, responding to a criticism of his hypothesis that cancer is a problem of energy. “A man who knows nothing at all about engines, their structure and their purpose may discover the difference. He may, for example, smell it.”

The “complete combustion,” in Warburg’s analogy, is respiration. The “incomplete combustion,” turning nutrients into energy without oxygen, is known as fermentation. Fermentation provides a useful backup when oxygen can’t reach cells quickly enough to keep up with demand. (Our muscle cells turn to fermentation during intense exercise.) Warburg thought that defects prevent cancer cells from being able to use respiration, but scientists now widely agree that this is wrong. A growing tumor can be thought of as a construction site, and as today’s researchers explain it, the Warburg effect opens the gates for more and more trucks to deliver building materials (in the form of glucose molecules) to make “daughter” cells.

Top of Form

Bottom of Form

If this theory can explain the “why” of the Warburg effect, it still leaves the more pressing question of what, exactly, sets a cell on the path to the Warburg effect and cancer. Scientists at several of the nation’s top cancer hospitals have spearheaded the Warburg revival, in hopes of finding the answer. These researchers, typically molecular biologists by training, have turned to metabolism and the Warburg effect because their own research led each of them to the same conclusion: A number of the cancer-causing genes that have long been known for their role in cell division also regulate cells’ consumption of nutrients.

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. In Thompson’s analogy, the Warburg effect can be thought of as a social failure: a breakdown of the nutrient-sharing agreement that single-celled organisms signed when they joined forces to become multicellular organisms. 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. But Thompson’s search for those mutations didn’t lead to an entirely new discovery. Instead, it led him to AKT, a gene already well known to molecular biologists for its role in promoting cell division. Thompson now believes AKT plays an even more fundamental role in metabolism.

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. When Thompson presents his research to high-school students, he shows them a slide of mold spreading across a piece of bread. The slide’s heading — “Everyone’s first cancer experiment” — recalls Warburg’s observation that cancer cells will carry out fermentation at almost the same rate of wildly growing yeasts.

Just as Thompson has redefined the role of AKT, Chi Van Dang, director of the Abramson Cancer Center at the University of Pennsylvania, has helped lead the cancer world to an appreciation of how one widely studied gene can profoundly influence a tumor’s metabolism. In 1997, Dang became one of the first scientists to connect molecular biology to the science of cellular metabolism when he demonstrated that MYC — a so-called regulator gene well known for its role in cell proliferation — directly targets an enzyme that can turn on the Warburg effect. Dang recalls that other researchers were skeptical of his interest in a housekeeping enzyme, but he stuck with it because he came to appreciate something critical: Cancer cells can’t stop eating.

Unlike healthy cells, growing cancer cells are missing the internal feedback loops that are designed to conserve resources when food isn’t available. They’re “addicted to nutrients,” Dang says; 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: It’s not that other types of alterations can’t arise first, but rather that, when they do, the incipient tumors lack the access to the nutrients they need to grow. Dang uses the analogy of a work crew trying to put up a building. “If you don’t have enough cement, and you try to put a lot of bricks together, you’re going to collapse,” he says.

Photo

 

Warburg’s Workshop: The Kaiser Wilhelm Institute for Cell Physiology (now part of the Max Planck Society) in Berlin, 1931.CreditSource photograph from archives of the Max Planck Society, Berlin.

Metabolism-centered therapies have produced some tantalizing successes. Agios Pharmaceuticals, a company co-founded by Thompson, is now testing a drug that treats cases of acute myelogenous leukemia that have been resistant to other therapies by inhibiting the mutated versions of the metabolic enzyme IDH 2. In clinical trials of the Agios drug, nearly 40 percent of patients who carry these mutations are experiencing at least partial remissions.

Researchers working in a lab run by Peter Pedersen, a professor of biochemistry at Johns Hopkins, discovered that a compound known as 3-bromopyruvate can block energy production in cancer cells and, at least in rats and rabbits, wipe out advanced liver cancer. (Trials of the drug have yet to begin.) At Penn, Dang and his colleagues are now trying to block multiple metabolic pathways at the same time. In mice, this two-pronged approach has been able to shrink some tumors without debilitating side effects. Dang says the hope is not necessarily to find a cure but rather to keep cancer at bay in a “smoldering quiet state,” much as patients treat their hypertension.

Warburg, too, appreciated that a tumor’s dependence upon a steady flow of nutrients might eventually prove to be its fatal weakness. Long after his initial discovery of the Warburg effect, he continued to research the enzymes involved in fermentation and to explore the possibility of blocking the process in cancer cells. The challenge Warburg faced then is the same one that metabolism researchers face today: Cancer is an incredibly persistent foe. Blocking one metabolic pathway has been shown to slow down and even stop tumor growth in some cases, but tumors tend to find another way. “You block glucose, they use glutamine,” Dang says, in reference to another primary fuel used by cancers. “You block glucose and glutamine, they might be able to use fatty acids. We don’t know yet.”

Given Warburg’s own story of historical neglect, it’s fitting that what may turn out to be one of the most promising cancer metabolism drugs has been sitting in plain sight for decades. That drug, metformin, is already widely prescribed to decrease the glucose in the blood of diabetics (76.9 million metformin prescriptions were filled in the United States in 2014). In the years ahead, it’s likely to be used to treat — or at least to prevent — some cancers. Because metformin can influence a number of metabolic pathways, the precise mechanism by which it achieves its anticancer effects remains a source of debate. But the results of numerous epidemiological studies have been striking. Diabetics taking metformin seem to be significantly less likely to develop cancer than diabetics who don’t — and significantly less likely to die from the disease when they do.

Near the end of his life, Warburg grew obsessed with his diet. He believed that most cancer was preventable and thought that chemicals added to food and used in agriculture could cause tumors by interfering with respiration. He stopped eating bread unless it was baked in his own home. He would drink milk only if it came from a special herd of cows, and used a centrifuge at his lab to make his cream and butter.

Warburg’s personal diet is unlikely to become a path to prevention. But the Warburg revival has allowed researchers to develop a hypothesis for how the diets that are linked to our obesity and diabetes epidemics — specifically, sugar-heavy diets that can result in permanently elevated levels of the hormone insulin — may also be driving cells to the Warburg effect and cancer.

The insulin hypothesis can be traced to the research of Lewis Cantley, the director of the Meyer Cancer Center at Weill Cornell Medical College. In the 1980s, Cantley discovered how insulin, which is released by the pancreas and tells cells to take up glucose, influences what happens inside a cell. Cantley now refers to insulin and a closely related hormone, IGF-1 (insulinlike growth factor 1), as “the champion” activators of metabolic proteins linked to cancer. He’s beginning to see evidence, he says, that in some cases, “it really is insulin itself that’s getting the tumor started.” One way to think about the Warburg effect, says Cantley, is as the insulin, or IGF-1, signaling pathway “gone awry — it’s cells behaving as though insulin were telling it to take up glucose all the time and to grow.” Cantley, who avoids eating sugar as much as he can, is currently studying the effects of diet on mice that have the mutations that are commonly found in colorectal and other cancers. He says that the effects of a sugary diet on colorectal, breast and other cancer models “looks very impressive” and “rather scary.”

Elevated insulin is also strongly associated with obesity, which is expected soon to overtake smoking as the leading cause of preventable cancer. Cancers linked to obesity and diabetes have more receptors for insulin and IGF-1, and people with defective IGF-1 receptors appear to be nearly immune to cancer. Retrospective studies, which look back at patient histories, suggest that many people who develop colorectal, pancreatic or breast cancer have elevated insulin levels before diagnosis. It’s perhaps not entirely surprising, then, that when researchers want to grow breast-cancer cells in the lab, they add insulin to the tissue culture. When they remove the insulin, the cancer cells die.

“I think there’s no doubt that insulin is pro-cancer,” Watson says, with respect to the link between obesity, diabetes and cancer. “It’s as good a hypothesis as we have now.” Watson takes metformin for cancer prevention; among its many effects, metformin works to lower insulin levels. Not every cancer researcher, however, is convinced of the role of insulin and IGF-1 in cancer. Robert Weinberg, a researcher at M.I.T.’s Whitehead Institute who pioneered the discovery of cancer-causing genes in the ’80s, has remained somewhat cool to certain aspects of the cancer-metabolism revival. Weinberg says that there isn’t yet enough evidence to know whether the levels of insulin and IGF-1 present in obese people are sufficient to trigger the Warburg effect. “It’s a hypothesis,” Weinberg says. “I don’t know if it’s right or wrong.”

During Warburg’s lifetime, insulin’s effects on metabolic pathways were even less well understood. But given his ego, it’s highly unlikely that he would have considered the possibility that anything other than damaged respiration could cause cancer. He died sure that he was right about the disease. Warburg framed a quote from Max Planck and hung it above his desk: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die.”

Sam Apple is the author of the memoir “American Parent” and teaches journalism at the University of Pennsylvania.

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A version of this article appears in print on May 15, 2016, on Page MM64 of the Sunday Magazine with the headline: Starving the Beast. 

 

https://www.nytimes.com/2016/05/15/magazine/warburg-effect-an-old-idea-revived-starve-cancer-to-death.html