[h=3]
If cancer is not a genetic disease then what is it?[/b]If James Watson was filled with optimism in the summer of 2009, then he was equally filled with scathing pessimism in the winter of 2012. It seemed as though cancer had once again dangled a carrot in front of him, only to violently pull it back as he cautiously reached out with hope. Watson expressed his frustration in a paper published around the world. The paper appeared the day after the country's top cancer organizations acknowledged in an annual report that we're making agonizingly slow progress in reducing the disease's death rate. Watson's frustration this time was not an undertone but instead boiled over – declaring, “the ‘curing' of many cancers seems now to many seasoned scientists an even more daunting objective than when the ‘War on cancer' was started by President Nixon in December 1971.” The seemingly random nature of the mutations coming from the TCGA caught everybody by surprise.But something new came out of Watson's paper, something he had also addressed in a recent speech at Yale University – the defective metabolism of cancer – even going as far to call it the ‘Achilles Heel' of the cancer cell.
Let me tell you why this is important — long before cancer was thought to be a genetic disease, resulting from mutations to key oncogenes, it was thought to be a metabolic disease, resulting from defective metabolism. Metabolism is a general word describing all of the chemical reactions the cell undergoes to generate energy. However, the metabolic theory was unceremoniously discarded when it was found that the DNA of cancer cells, the profound molecule Watson had just reveled to the world, contained mutations.
[h=2]Long before cancer was thought to be a GENETIC DISEASE, resulting from mutations to key oncogenes, it was thought to be a METABOLIC DISEASE, resulting from defective metabolism.[/b]The metabolic theory of cancer goes way back to 1924 in Berlin, Germany, — and a curious biochemist named Otto Warburg. While working in his lab Warburg noticed something strange about cancer cells – critically, he noticed they had difficulty using oxygen to generate energy.
Warburg was not your average scientist, not only did he win a Nobel Prize, but he was nominated an unprecedented three times for three separate achievements. Remarkable in his brilliance and productivity, Warburg single handedly advanced human physiology by leaps and bounds in the early twentieth century. Since Warburg was Jewish, he was forced by the Nazi regime in Germany to decline a second Nobel Prize Award in 1944. Nevertheless, the government did not imprison Warburg, because it was believed Hitler was terrified of cancer, and Warburg was the world's foremost expert at the time.
Unlike the mutational profile of a cancer cell's DNA, the profoundly altered metabolism of cancer cells, Warburg documented, was consistent from one cancer to the next, it was a pervasive feature of the cancer cell.
A healthy cell produces 89% of its energy using oxygen, and 11% through non-oxidative metabolism (non-oxidative metabolism is also known as fermentation.) While cancer cells continue to produce energy through non-oxidative pathways even in the presence of oxygen – this is called the Warburg effect. The observation that the Warburg effect was such a consistent and dominate aspect of cancer, spanning the entire spectrum of the disease, led Warburg to propose a hypotheses assigning damaged metabolism as the origin of the disease . This is how Warburg described the metabolic origin of cancer in 1924, “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 the fermentation of sugar.”
Oxidative energy production is far more efficient than fermentation. Almost 20 times more energy is released when glucose is completely oxidized, as opposed to when it is fermented. Oxidative energy production takes place in a cellular organelle called the mitochondria. The mitochondria are commonly referred to as the cellular “power plants” because their primary function is to supply the body with all its energy requirements. The metabolic theory of cancer contends that the disease begins with damage to the mitochondria thus impairing oxidative energy production — the cell is then forced to produce energy through fermentation in order to survive. Because a tumor cell's mitochondria are damaged, and are therefore forced to generate energy by such an inefficient pathway, they have to consume much more glucose to remain viable. A glance at a PET scan, which uses a radioactive labeled glucose analog to image cancer, provides stunning visual evidence of the voracious appetite tumor cells have for glucose compared to normal tissue.
[h=2]A glance at a PET scan, which uses a radioactive labeled glucose analog to image cancer, provides STUNNING visual evidence of the voracious appetite tumor cells have for GLUCOSE compared to normal tissue.[/b]Clifton Leaf's all-consuming effort to put his finger on the fundamental issues preventing progress in the treatment of cancer for his award-wining 2004 article, ‘Why we're Losing the War on Cancer' was no simple task. He asked dozens of researchers, physicians, and epidemiologists at leading cancer hospitals around the country; pharmacologists, biologists, and geneticists at drug companies and research centers; officials at the FDA, NCI, and NIH; fundraisers, activists, and patients. During three months of interviews in Houston, Boston, New York, San Francisco, Washington, D.C., and other cancer hubs. Yet virtually all these experts offered testimony that Leaf found, when taken together, describes a dysfunctional “cancer culture”–a groupthink that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs; that fosters isolated (and redundant) problem solving instead of cooperation; and rewards academic achievement and publication over all else. Leaf's overall conclusion is that progress has been so slow because:
A. Cancer is a brutally complex problem.
B. Terrible models – the mouse models researchers use to study cancer do not accuracy represent the real disease.
C. Research grants incentivize researchers to focus on narrow pathways.
D. A shortage of good, creative ideas, and a groupthink mentality
What if the reason progress has been so terribly elusive is not only because of the reasons Leaf has identified above, but also, and more importantly, because researchers have gotten the theory of cancer wrong? What if this is the
deep-fundamental problem — festering below the surface, hidden in plain sight – an invisible straitjacket restraining progress? It is difficult to explain why the death rates would be the same today as they were in 1950 unless something was
profoundly wrong. How on earth could the tremendous resources dedicated to new therapies – not just at the NCI – but also at almost every major pharmaceutical company around the world not have produced
some meaningful results? Just maybe, as Warburg proposed in 1924; cancer
really is a metabolic disease, and researchers throughout the world have been looking in the wrong place.
[h=3]
Just One Shade Off[/b]Early on, once it was clear the data from the TCGA did not support the Somatic Mutation Theory of Cancer; Dr. Thomas Seyfried of Boston College didn't wait around for the data to make sense like so many others. Instead he and his students dove head-first into an exhaustive review of 100 years of cancer research, attempting to answer the still terribly elusive question: What is the true nature of cancer? With over 2.8 million publications dedicated to understanding the obscure molecular mechanics operating within the cancer cell, cancer research lends itself well to a back-room detective approach – with papers scattered all over the floor and tacked to walls, scouring the evidence waiting for patterns and clues to emerge. His answer – Warburg was right; cancer originates and is driven by defective metabolism. The culmination of his efforts was a very provocative book titled “Cancer as a Metabolic Disease.” The comprehensive work was released in 2012 to much acclaim and controversy. If Dr. Seyfried intended to shock, and rattle-the-cage of the cancer community, then he certainly achieved his goal. The book pounds home the message chapter after chapter that cancer, as Warburg proposed, originates and progresses by damage to the cell's mitochondria. Seyfried calls the mutations observed in the nuclear DNA of cancer “red herrings” that have little to do with the origination of the disease.
Still slightly humming with jet lag, I paced the hallways of Boston College's Higgins Hall waiting for Dr. Seyfried. Early for our meeting, but not wanting to break the almost churchlike morning silence by knocking on his office door, I just stood there – transfixed, if not slightly intimidated by the posters decorating the hallway, summarizing decades of cancer research. I was startled when the office door suddenly flung open.
After the obligatory introductions and small talk Seyfried launched into something more substantive, “My most creative time is in the morning — that's when I do my best work,” just as the topic switched to cancer, Seyfried abruptly halted, “I'm late for my graduate class on cancer. Would you like to sit in?” “Of course,” I answered.
“The professors in your other molecular biology and genetics classes will tell you that mutations to genes cause cancer because that is what they were told, and that's what the professors before them were told, and what their textbook said,” Seyfried told the graduate students, now talking quite fast as he was unable to contain his own enthusiasm. “Don't believe them, look at the evidence and make up your own mind.” As Seyfried lectured he filled the room with an infectious and palatable excitement. After class we walked down the atrium balcony to his lab. Students stopped him along the way asking questions. Once in the lab we sat down with one of his graduate students and for the remainder of the day, the two of them laid out their argument for why the cancer community has mischaracterized the true nature of cancer, and that Otto Warburg had it right — cancer is a disease of metabolism. As the students came and went you couldn't help detect the feeling one might feel at an exciting start-up company. There was energy of innovation, and a sense that here, in Seyfried's lab, there was a sort-of secret that nobody else yet knew but them – they were positive they had identified the true nature of cancer.
It is not difficult to see how it could happen. Nature, with her sardonic sense of humor, according to Seyfried, orchestrated the perfect cover up. When you listen to Seyfried describe it – in exhaustive detail – it seems as though the metabolic theory was covered up by a master criminal — every piece of evidence manipulated to divert attention from the real perpetrator of the crime to an innocent bystander. The differences between the two competing theories are subtle. Rather than existing in sharp contrast, they are just one shade off.
The same agents that damage DNA; cigarette smoke, chemicals, and other carcinogens also damage mitochondria. Once damaged the mitochondria send out signals that activate a series of important oncogenic pathways, altering huge swaths of the genomic landscape, waking-up some genes, putting others to sleep, but when taken together, manifest in uncontrolled proliferation and genomic instability — the most salient features of cancer. The most important point, the crux of the entire issue, is that the mutations thought to be the decisive event, supersede metabolic dysfunction. These mutations, although just a side effect of the true origin of the disease, could easily be mistaken as the cause – sending researchers on a multi-billion dollar and multi-decade wild goose chase.
Inherited cancer risk has been historically cited as evidence in support of the genetic theory (inherited cancers only account for 5% to 7% of all cancers, the vast majority arises spontaneously). When challenged by the assertion that inherited cancer risk provides irrefutable evidence that cancer is of genetic origin, Dr. Seyfried, one by one, explains how inherited cancer causing genes manifest in damage to the mitochondria, thus precipitating cancer through metabolism – again the perfect cover up. It is like a detective, who after an arduous investigation, finds evidence pointing to 10 different people whom appear to be responsible for killing members of certain afflicted families – but when the detective digs deeper, he finds out the 10 people were ordering the hits through the same hit-man.
Take for example the BRCA1 mutation which has recently caught the public's attention as the mutation responsible for Angelina Jolie's decision to undergo a double mastectomy. Inheriting a faulty BRCA1 gene jumps the risk of acquiring breast cancer in a women's lifetime to 60% from 12%. Among other cellular duties, BRCA1 is involved in mitochondrial function, including the biogenesis of new mitochondria. Therefore an inherited mutation to BRCA1, rendering its protein product defective, would manifest in reduced mitochondrial capacity, the metabolic origin of cancer.
Even Gleevec, the one successful targeted drug, is often cited as proof of principle that targeting drugs to the mutated products of oncogenes is the right strategy. A closer look reveals that although Gleevec binds to a mutated protein, it exerts its efficacy by altering a pathway that is up-regulated by defective metabolism. Says Seyfried: “Gleevec simply highjacks a mutation that serendipitously down-regulates an oncogenic pathway turned-on by damaged mitochondria.”
[h=2]“Gleevec simply HIGHJACKS a mutation that serendipitously down-regulates an oncogenic pathway turned-on by damaged mitochondria.” Dr. Thomas Seyfried[/b]Proponents of the metabolic theory of cancer are quick to point out that the circumstantial evidence in favor of the metabolic theory is everywhere. For example, the one novel gene discovered so far by CGAP, the one referenced earlier as the most significant finding to come out of the CGAP is isocitrate dehydrogenase, a gene which encodes one of the crucial components of oxidative energy production – linking a mutated oncogene to defective metabolism.
And then there is the curious case of Metformin. Researchers were scratching their heads when they found out patients with type 2 diabetes, who were taking the drug metformin to lower their blood-sugar, had substantially reduced rates of cancer. Turns out the blood-sugar lowering drug not only prevents cancer, but can also treat cancer – unequivocally suggesting a connection between metabolism and cancer.
People who practice caloric restriction or periodic fasting have been shown to have lower cancer rates. Why? When calories are reduced to a certain threshold the body initiates a process called autophagy (self-digestion). Autophagy is a cellular process that consumes damaged cellular components, including damaged mitochondria, and will use the digested components to meet energy requirements, a cleaning house process if you will — cleaning out the damaged mitochondria that are the incipient seeds of malignancy.
Metastasis is unquestionably the most important feature of cancer resulting in 90% of cancer deaths. Metastasis involves aggressive and versatile cancer cells with the ability to degrade membranes, enter into the circulatory system, invade into new sites, change shape, and secrete growth factors and cytokines. The genetic theory of cancer, of course, proposes critical sequential-mutations will result in a less aggressive cancer acquiring all these metastatic features – random mutations that result in a tremendously complex
gain of function. Not surprisingly, a TCGA follow up study, attempting to identify metastatic specific mutations found none.
[h=2]Proponents of the metabolic theory of cancer are quick to point out that the CIRCUMSTANTIAL EVIDENCE IN FAVOR of the metabolic theory is everywhere.[/b]It turns out tumors are already full of cells called tumor-associated macrophages (TAMs) that have all of the metastatic qualities mentioned above. TAM's are tough, gritty immune cells that are already capable of infiltrating tissues, hitch-hiking rides in the circulatory system, and setting-up camp in different organs. It is well documented that cancer cells fuse with TAM's in the context of the chaotic tumor microenvironment. In doing so, TAMs acquire all the genetic and cytoplasmic material present in cancer cells, including damaged mitochondria, marching these cells one step closer to malignancy. The chronic and highly-inflammatory microenvironment will continue to damage TAM's mitochondria unleashing cells capable of full blown metastasis. The metabolic theory provides a simple and elegant explanation for metastasis that is in complete harmony with empirical evidence — in complete contrast to the genetic theory. As Einstein said, “The simplest explanation is usually the correct one.”
[h=3]
Fertilizer to a Gardener[/b]What about treatment? Rather than targeting elusive, shape-shifting, here-in-one-case, gone-in-the- next, mutations – the metabolic theory of cancer provides researchers with one big-beautiful-target – cancer cells of all types, regardless of the tissue of origin, have to ferment glucose for energy because of their damaged mitochondria, normal cells have other options. In the end, any theory used to explain cancer is only as good as the therapies that flow from it -this is where the metabolic theory leaves the theoretical and enters the real world.
If cancer is caused by defective metabolism then the first and most obvious place to implement treatment is through diet – after all, diet is the quickest and surest way to alter metabolism. It turns out there is a way to manipulate the diet that dramatically reduces the blood glucose that cancer cells so heavily rely on, forcing the body to generate new fuels from fat called ketone bodies — a fuel source that cancer cells are unable to utilize because they can only be burned through oxidative pathways, in healthy fully-functional mitochondria – cancers ‘Achilles Heel' as Watson put it.
[h=2]What about treatment? Rather than targeting ELUSIVE, shape-shifting, here-in-one-case, gone-in-the- next, mutations – the metabolic theory of cancer provides researchers with one BIG-beautiful-target.[/b]Relegated as an obscure side note in medical journals, the ketogenic diet was observed to be an effective, if not strange therapy for pediatric epilepsy in the 1920's, around the same time Warburg was noticing the striking metabolic deficiencies of the cancer cells in his petri dishes. However, once anticonvulsive drugs were developed in the 40's, it was largely forgotten.
The current resurrection of the ketogenic diet, this time to treat cancer, dubbed the restricted-ketogenic diet, was born from the work in Dr. Seyfried's lab. Using very aggressive mouse models of brain cancer, they have achieved staggering results — and they were achieving them simply through diet.
The restricted ketogenic diet restricts overall calories and virtual eliminates carbohydrates – driving down blood glucose from about 100 mg-dl to around 55 or 65 mg-dl, forcing the liver to begin manufacturing small molecules called ketone bodies from fat, taking over the role of glucose as a circulating fuel. “Once a patient is in this state of ketosis their cancer cells are put under tremendous pressure because they are being starved for energy while healthy cells simply switch-over to burning ketone bodies in their intact and functional mitochondria,” says Seyfried.
“The parallel history of the Ketogenic diet as a cancer treatment, and the ketogenic diet as a treatment for epilepsy, are hauntingly similar,” says Hollywood movie director, writer, and founder of the world-renowned Charlie Foundation, Jim Abrahams.
Nobody knows the history of the ketogenic diet better than Jim. In the mid-1990s, before he had ever heard of the ketogenic diet, Jim was at the end-of-his-rope. His son Charlie's severe epilepsy wasn't responding to drugs, and 5 different neurologists offered little in the way of hope. “Once I heard about the ketogenic diet we immediately tried it – within days Charlie was seizure free. I was baffled and angry at the time. How could the public not know about this?” Jim's efforts to inform the public included an appearance on NBC's Dateline program and ‘First Do No Harm', a made-for-television film starring Meryl Streep, and ultimately the formation of the Charlie Foundation. “When I started the Charlie Foundation, I thought it would be a straight line – we would inform the public of this incredibly effective dietary treatment for epilepsy and that would be it – unfortunately it just wasn't that simple. Today, all the myths that had been used to detract from the diet have been disproven. Efficacy has been scientifically established, long term side effects have been dispelled, palatability has been dramatically enhanced, and difficultly of administration has been equally dramatically reduced. The biggest problem today is trying to figure out how hospitals can reimburse trained ketogenic diet dietitians for their time.”
“The efficacy of this diet is really remarkable,” says Dr. Seyfried, “If one was able to patent and package the ketogenic diet as a pill for cancer it would be a blockbuster. It would be all over the media. The irony is because it is free, nobody is interested.” Dr. Seyfried and his colleagues, like Dr. Dominic D'Agostino of the University of South Florida have seen the tremendous power of the ketogenic diet first-hand. Says D'Agostino: “We have seen complete remissions – despite tremendous odds.”
[h=2]“The efficacy of this diet is really remarkable. If one was able to patent and package the ketogenic diet as a pill for cancer it would be a blockbuster.” Dr. Thomas Seyfried[/b]It's not hard to find those who will testify on behalf of the diets cancer fighting prowess. Like Miriam Kalamian, a highly-energetic parent and advocate of the ketogenic diet, who says it saved her son's life, “In December of 2004, our 4 year old son Raffi was diagnosed with a brain tumor. After three surgeries and several failed drug protocols, it was clear that the tumor was winning. Our little fighter had done everything we asked of him, but he was no match for his opponent. In March of 2007, we discovered research from Boston College that had demonstrated that a calorically restricted ketogenic diet could slow progression of brain tumors….We had nothing to lose, so with the support of his pediatrician and oncologist, Raffi began a restricted ketogenic diet concurrent with a low-dose chemotherapy drug (the same drug that failed to work previously). Amazingly, the tumor shrank by 15% in the first 3 months! Chemo was discontinued in December of 2007 and Raffi continued with the ketogenic diet as his sole therapy for 3 more years.”*
And Dr. Fred Hatfield, who was sent home to die. “The bones in my entire pelvic girdle were riddled with metastatic prostate cancer. I was confined to a wheelchair – the bones had cracks in places. Three separate doctors had given me three months to live. I heard about Dr. D'Angostino and the ketogenic diet and decided why not give it a try? The next scan I had was completely clear.” I called Dr. Hatfield to see how he was doing recently; he had to call me back because he was in the middle of putting up wall-paper. “All clear, I make sure I go into ketosis at least once a month. Metabolic therapy saved my life.”
Miriam Kalamian and Dr. Hatfield are far from alone. Many desperate cancer patients have found out about the ketogenic diet and are treating themselves, some with remarkable success. You will find them on internet-forums, through emails, they are a silent but growing community, and many are confused why doctors know so little about this.
“Metabolic therapy is defiantly gaining traction, the number of emails I receive from people interested in treatment, or that are already implementing treatment, has increased exponentially,” says Dr. Seyfried. And this is not an isolated observation – everybody involved with the ketogenic diet says the same thing.
“We are changing our name,” says Jim Abrahams of the Charlie Foundation, “from the Charlie Foundation to Help Cure Pediatric Epilepsy, to the Charlie Foundation for Ketogenic Therapies. It used to be the only people that contacted us where those interested in the diet for epilepsy, now about half the people that contact us are interested in the ketogenic diet for other afflictions, including cancer.”
“Once you frame cancer in the light of a metabolic disease the treatment options get exciting. The ketogenic diet is just the first piece of low-hanging fruit – the drugs that target cancer's defective metabolism are just getting started – and when you combine the two — that's when things get really interesting,” says Dr. Seyfried. The important point emphasized by scientists who study the combination of the ketogenic diet combined with drugs that target metabolism – is that the ketogenic diet differentiates in a way that no chemotherapeutic drug on the market is able to – the ketogenic diet makes healthy cells healthier and sick cells sicker – allowing a synergistic effect when adjunctive agents are utilized. It prepares the therapeutic landscape to be more receptive to additional treatments that target metabolism – When taken together as a comprehensive therapeutic strategy; the ketogenic diet could be thought of as primer to a painter, or fertilizer to a gardener.
[h=2]When taken together as a comprehensive therapeutic strategy; the ketogenic diet could be thought of as PRIMER to a painter, or FERTILIZER to a gardener.[/b]
[h=3]
Sitting on the Bench[/b]If there is a modern-day incarnation of the spirit, brilliance, and tenacity of Otto Warburg, then he is in the form of Dr. Peter Pedersen of John Hopkins School of Medicine in Baltimore. If the Warburg theory of cancer was a raging fire in the early 20[SUP]
th[/SUP] century, then it dimmed to a single ember by the middle of the century – an ember that Dr. Petersen alone nurtured and kept alive. “I've watched interest in the metabolism of cancer go down to zero in the 70's, but now interest is returning. There were times in my early career when I felt almost alone in considering energy metabolism as important to the cancer problem. I even remember one of my colleagues, an expert in DNA technology, dumping Lehninger's “Warburg Flasks” in the trash as relics of a bygone era in cancer research.”
Nevertheless, Pedersen undeterred, kept on with the heavy-lifting — mapping the critical molecular architecture in the inner-city of cancer's defective metabolism. Once his lab had elucidated the pathologically altered infrastructure embedded within the cancer cell's mitochondrial outer-membrane, they began to screen for drugs that would target and exploit the structural differences Pedersen had identified between normal and cancerous cells. “After screening only nine compounds we found one, called 3BP, that was incredibly powerful. Pharmaceutical companies typically screen thousands and thousands of compounds before finding one that might be effective – we only went through nine.” When his lab began to test 3BP in rats however, they encountered a new problem. “One problem we have in the lab is what to do with all the rats we test 3BP on because we cure them all – we had to figure out how to take care of them all,” says Pedersen.
In the winter of 2009 it was time for 3BP to leave the parental confines of Pedersen's laboratory and enter the real-world testing ground – from lab side to bedside — 3BP was about to enter its first human cancer patient. The patient was a 16 year old with hepatocellular carcinoma (HCC), i.e., liver cancer. 3BP was administered more than half a dozen times about 2 weeks to a month apart. Again, the problem they encountered was the staggering efficiency with which 3BP killed cancer cells.
Initially, the patient presented with a large tumor burden in his liver as 3BP swiftly destroyed massive numbers of cancer cells with staggering speed the patient suffered from a transient case of tumor lysis syndrome – a toxic collateral burden imposed on the body from the simultaneous death and release of malignant shrapnel into the bloodstream. Luckily, the tumor lysis syndrome proved to be transient, and soon regeneration was initiated in the young patient's liver. The patient started to retrain his body to perform normal activities, i.e., normal eating, sleeping, walking, etc. While the fresh liver regeneration was in process, the patient had to take some antibiotics due to an unexpected pneumonia infection. Unfortunately, his regenerating liver could not detoxify the administered antibiotics and he passed away. If such infection could have been prevented, the outcome may have forced the research community to pay closer attention.
“3BP doesn't just slow growth like the vast majority of chemotherapeutic agents – it explodes cancer cells. In the future we have to be very careful as we move it through the clinic because of its incredibly powerful and explosive nature,” Says Dr. George Yu of George Washington University, who is as eager to see 3BP enter clinical trials as anybody. “I would love to see 3BP in conjunction with a restricted ketogenic diet, because the diet is pro-apoptotic, and will alter the way the cancer cells die – they will die more orderly, with less inflammation and toxic release.”
[h=2]“3BP doesn't just slow growth like the vast majority of chemotherapeutic agents – it explodes cancer cells. In the FUTURE we have to be very careful as we move it through the clinic because of its incredibly powerful and explosive nature,” Dr. George Yu[/b]3BP was born from theoretical elegance – a product of human ingenuity – a child of logic and reason. But as a passive observer — with no dog in the fight — I can't help but compare 3BP to an all-star slugger that came to a struggling team out of nowhere, a player that looks capable of hitting a home run virtually every time at bat – yet for some unknown reason, he is still just sitting on the bench.
3BP is not the only promising player sitting on the bench. Other journal documented case studies exist of cancer patients ordering the handful of compounds known to target tumor metabolism from chemical supply houses and administer it to themselves – achieving complete and enduring remissions. One such study is of dichloroacetate (DCA), a metabolism targeting drug that received a spike of media attention after
New Scientist magazine published an article titled “Cheap, ‘safe' drug kills most cancers,” only to again fall to obscurity after funding proved nonexistent for the cheap drug. One such study reports on a man fighting for his life against non-Hodgkin's lymphoma. After the state of the art chemotherapy failed, and the cancer returned aggressively months later, he decided to treat himself with DCA – not wanting to go through the nausea and fatigue caused by the chemotherapy again. After doing his own research, the patient began to mix 1000 mg of DCA into a bottle of Mt. Dew every morning – “Within 2 weeks of starting this regimen, the patient reported significant reduction in night sweats, low grade fever, anorexia and fatigue. One month after initiation of the DCA protocol, the neck nodes were noticeably smaller, and at 2 months no nodes were palpable. At 71 days into the DCA protocol, complete resolution of all systemic symptoms had occurred. The patient reported a good energy level and appetite, the ability to sleep well and no side effects.”
“If you were to plot a graph of time and money spent versus the realized results for all the treatments born from the Somatic Mutation Theory of Cancer it would tell you unequivocally you're insane to keep throwing good money at this flawed scientific paradigm,” says Dr. Seyfried, “If you were to plot the same graph – time and money spent versus results seen so far for metabolic treatments — the promise and potential would be obvious to a child.”
“It is very difficult not to be cynical about this stuff – but it usually comes down to money,” says Jim Abrahams, “the hard reality is diet is free, so there is little interest from anybody – the usual channels of funding (pharmaceutical companies) just don't give a rat's ass.” The drugs that target the metabolism of cancer face the same challenges as the ketogenic diet – most are non-patentable, so there is little interest – the 100 million plus bill to take a drug from the lab through the clinic is usually picked up by pharmaceutical companies — a bill that is typically paid back in massive multiples of the original cost once a patent is received.
[h=2]“If you were to plot a graph of time and money spent versus the realized results for all the treatments born form the Somatic Mutation Theory of Cancer it would tell you unequivocally you're insane to keep throwing good money at this FLAWED scientific paradigm. If you were to plot the same graph – time and money spent, versus results seen so far for metabolic treatments — the promise and potential would be obvious to a child.” Dr. Thomas Seyfried[/b]As a consequence the clinic for these therapies has morphed into the public at large. Advocates that have heard the claims from others, and then in-turn demand it from their doctors.
Sometimes in medicine a few adventurous individuals end up teaching the entire medical complex – the tail wags the dog. Like Barry Marshall, labeled a quack by the medical community for his claim that a yet unknown species of bacteria, an organism that according to convention, could not exist in the acidic environment of the stomach, was the true cause of ulcers rather than stress — the accepted, but ambiguous perpetrator. Once Marshall was convinced he had isolated the elusive bacteria, he grew it in a flask and drank it. The highly publicized ulcer he gave himself was documented in a medical journal – unequivocally proving to the establishment that bacteria (now identified as
helicobacter pylori) can cause ulcers – Marshall was later awarded a Nobel Prize.
[h=3]
Dark matter discovered?[/b]When Bert Vogelstein postulated the existence of cancer biology's ‘dark matter' the most obvious possibility he suggests, are epigenetic drivers. Epigenetics is a term used to describe all of the ‘other' influences that operated on DNA beyond the fixed genetic code. Unlike genetic code, epigenetic drivers are plastic, fluid, and transient forces that influence the expression of genes. The crucial link, the one process that Warburg was unable to identify that would have tied his theory of cancer into a single and beautiful unified-explanation of cancer, from the beginning to the end, is epigenetic signaling. Dr. Seyfried and others propose that chronic and persistent damage to cellular mitochondria ultimately triggers an epigenetic signal from the mitochondria to the nuclear DNA, altering the expression of a plethora of key cancer causing genes – a classic epigenetic system
. The question then begs to be asked;
could the metabolic theory be Vogelstein's elusive dark matter?
Could it really be possible that so many brilliant minds have gotten this wrong? History provides the perspective to approach this question with – every generation thinks they are on the cutting-edge of modern technology – when in truth; our reference frame is just a blink-of-an-eye in the continuum of time. Without question, some medical student, hundreds of years from now, will read about the way we treated cancer patients, and feel a sharp-pang of empathy for our unenlightened and barbaric methods that so many suffered through and died from. The cancer-research medical complex, with its massive infrastructure, all the investment, and livings derived from it – from the businessmen and salesmen, to the doctors and nurses, is as encompassing as a black-hole, and struggles to move with the inertia of an arctic glacier. Somewhere in the middle of the colossal-beast are the research scientists, the secular high-priests of the entire system. With the faith of a devout congregation, we fill the tithe-tray with our tax-dollars and charitable donations, providing them with the resources they need to continue their arcane craft – and then we wait and hope, with faith and trust that they will find a cure. Their work so foreign, their degrees so prestigious –we deem them as infallible. Institutions like this are in many ways, the most likely to get a big-picture problem wrong. History is replete with examples of humanity getting huge scientific issues dead-wrong for protracted periods of time – often with large institutions behind it –persecuting the intrepid few who first question the
status quo. Remember, the earth was once flat and the sun orbited around it, blood-letting was thought to cure hemophilia, we cut holes into heads to release demons and we burned witches. Human progress is full of stops and starts, dead-ends and epiphanies, why would now be any different?
After traveling to Boston to interview Dr. Seyfried, he returned the favor, and generously accepted my invitation to come to my hometown, Rapid City, South Dakota, and speak to the M.D.'s at our regional hospital about the metabolic theory of cancer and the treatments derived from it. The morning before his lecture, we drove the 30 miles to Mt. Rushmore where we walked the scenic half-mile wooded path that meanders through the colossal chunks of granite and pine trees directly under the National Monument. It was a perfect June morning, mid 70's, with only an occasional cloud breaking the brilliant blue sky. The wandering, unhurried-path through the beautiful scenery inspired uninhibited conversation. “What do you think would happen if all the resources dedicated to the genetics of cancer were redirected to the metabolism of cancer?” I asked him. Dr. Seyfried paused, reflecting, “Ten years, I bet we could have real cures in 10 years if that were to happen.”
Travis M Christofferson M.S.
Founder,
SingleCauseSingleCure.Org
*Raffi passed away in April of 2013 – Mirrian is convinced Raffi may still be with us if he would have started the ketogenic diet from the time of diagnosis.
http://robbwolf.com/2013/09/19/origin-cancer/