Cancer is big business globally. Cynics – or realists, depending on your viewpoint – say it’s an industry ‘too prosperous to allow for a cure’. In 2015, the global market for annual sales of cancer drugs hit $100 billion. Estimates then were that it could reach $147 billion by 2018. It’s probably much more by now.
Yet despite the decades-long ‘war on cancer’ and billions spent on research, a cure is elusive. Of course, there has been progress. However, conventional treatment methods of chemotherapy and radiation have serious limitations, both in safety and efficacy. Even orthodox oncologists these days privately admit that these methods can be life-taking as much as life-saving.
Canadian nephrologist Dr Jason Fung has a special interest in cancer. Many of his patients have diabetes, a condition that significantly increases the risk of cancer. He says that there’s good reason why doctors lost the war. They cut the limbs of the facts to fit a popular – but wrong – theory. And still do. He says it’s time to stop lopping off limbs of inconvenient truths about the dread disease Fung turns to a myth of ancient Greece to explain why. – Marika Sboros
By Jason Fung
In Greek mythology, Procrustes was a son of Poseidon (god of the sea). He often invited passers-by to stay at his house to rest for the night. There he showed them to their bed. And if the guest was too tall, he would chop off their limbs until the bed fit just right.
If they were too short, he would stretch them on a rack until the bed fit just right. The great contemporary thinker and philosopher, Nassim Nicholas Taleb, often uses this allegory. But it is also appropriate to describe how some have tortured the facts to fit the theory of the Somatic Mutation Theory (SMT)
Theodor Boveri first postulated the basis of the SMT (that mutations cause cancer) in 1914. that was in his book, The Origin of Malignant Tumors. Boveri guessed that a combination of chromosomal defects could result in cancer. Looking at retinoblastoma, a rare eye tumour, Alfred Knudson suggested that a single mutation could result in cancer.
James Watson and Francis Crick’s 1950s discovery of the double helix of DNA lit a fire under genetic research. They made this theory the predominant cancer hypothesis for the next half-century.
Clearly, some tumours have a genetic predisposition, such as those that run in families. But 90–95% of cancers do not fall into this category. They are “sporadic”. But that doesn’t stop Procrustean researchers and doctors from stretching the facts to fit the “random genetic mutation” narrative.
The discovery of oncogenes and tumour suppressor genes led to the hope that cancer was one simple genetic mutation that could be targeted and corrected. In the case of chronic myelogenous leukaemia, this seems true, with a single chromosomal abnormality leading to disease.
A single genetic mutation could abnormally accelerate growth genes (oncogenes) or take the brakes off suppressor genes, with the same effect of uncontrolled growth. But a problem existed.
Between 1980 and 1990, researchers had identified hundreds and hundreds of these potential gene targets. If that was true, then why wasn’t everybody getting cancer?
Thought to be too simplistic for most common cancers, this led to the “two-hit hypothesis”. I learned that theory in medical school in the early 1990s.
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Sure, it was clear that cancers had mutations in their genes. But it was not at all clear that these mutations were primarily responsible for causing the disease. (See previous post — proximate vs ultimate causes).
So how many genetic changes were necessary for these cancers? In 1988, Bert Vogelstein, at Johns Hopkins Medical School started to investigate this question. Cancer seems to progress in a relatively orderly manner.
The discovery of pre-cancerous lesions, for example, in cervical cancer, allowed the development of the PAP smear. There was a long lag time between abnormal cells detected and true cancer, during which treatments could be used to prevent worse disease.
Colon cancer shows this same orderly progression — from a non-invasive, premalignant lesion called an adenoma to full-fledged cancer. This is the reason why screening colonoscopies are recommended — to catch these pre-cancerous lesions and deal with them before they become cancer. Indeed, colon cancer alone amongst the obesity-related cancers is showing decreasing incidence, possibly due to widespread use of screening.
Using colon cancer as an archetype, Vogelstein showed that genetic mutations accumulated in a manner parallel to the clinical progression. By intervening early and removing these precancerous lesions, you could hope to prevent future invasive disease.
One single mutation was not enough to cause the disease by itself. But as a cell accumulates a second or third mutation, it moved closer and closer to becoming cancer. If we could identify these 2 or 3 or 4 mutations, again, we have a target for treatment.
In 2003 the Human Genome Project was completed — the race to decipher the complete genetic code of a human being. Using this “normal” genome, a more ambitious project, The Cancer Genome Atlas, could compare the difference between malignant and normal cells and look for common mutations.
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Optimism for the future of cancer treatment was impossible to suppress. James Watson, the co-discoverer of DNA and Nobel laureate, wrote in a 2009 New York Times opinion that To Fight Cancer, Know the Enemy. The Atlas was the long-awaited cancer moon shot to know the enemy and bring the fight to him.
He wrote: “Beating cancer now is a realistic ambition because, at long last, we largely know its true genetic and chemical characteristics”. Watson, a member of the National Cancer Advisory Board since the time of President Nixon, was finally hopeful for the future.
But not everybody was convinced. Commentary by George Miklos in 2005 suggests: “Strap yourself in and get ready for some serious ‘more of the same’.” Many did not well appreciate his point at the time.
This new megaproject was only the ultimate culmination and continuation of a futile line of research that had so far gone exactly nowhere. The survival of cancer patients stagnated from 1973 to 1997, 25 years in which death from heart disease and stroke fell over 50%. From the viewpoint of Nixon’s war on cancer, it looked like we were losing.
Every area of technology — biotechnology, genetics, computers, semiconductors – was advancing at a pace never before seen in human history. Experts were developing network connectivity (Internet) at breakneck speed. Computing power was doubling every 18 months or so. Space travel was becoming a reality.
But cancer? It was a problem child. It wasn’t that we weren’t focused on the problem. Cancer research had consumed hundreds of billions of dollars already but common cancers were just as deadly as ever. Research had focused myopically on the search for oncogenes and tumour suppressor genes.
It’s not like there weren’t any researchers. Up to 2004, PubMed lists 1.56 million papers published on cancer. 1.56 million! The National Cancer Institute budget for 2004 was $4.7 billion. If you add in charities and other funding including pharmaceuticals, it was $14.4 billion. No, it wasn’t lack of money or lack of researchers that was the problem. It was the lack of fresh ideas.
Experts estimated the cost to be $1.35 billion over nine years of the project. Dr Craig Venter, who had just recently completed the Human Genome Project opined. “Diverting a billion or two dollars from other areas of research when it’s not clear what answer we’d get, there might be better ways to move cancer research forward”.
Prophetic, yes. Heeded, no.
Many already knew, at the project’s genesis, that tumours mutate rapidly and two cells even within the same tumour may have completely different mutations. In the New York Times, Dr Garth Anderson said: “We can spend $2 billion on something and get a lot of data, but I’m not convinced it will do us much good.”
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As the first reams of data started to pour in, the first inklings of the enormity of the challenge started to percolate. In individual breast or colon cancers, cells had not two, three or four 4 of the same mutations, but 50–80 mutations. Even brain cancer, which tends to occur in younger patients, had 40–50 mutations. But worse, the mutations were different between cancers.
Two clinically identical breast cancers will each have 50–80 mutations, but 50–80 completely different mutations from each other! It was genetic bedlam.
But the mind sees what it wants to see. Researchers saw genetic mutations everywhere so they made SMT to fit the Procrustean bed. Instead of individual mutations, they lumped them into mutation “pathways” so that they could identify multiple mutations within a single pathway as a single problem.
Then, others felt that certain mutations had no effect. So, there were “driver” mutations and “passenger” mutations that, all of a sudden, didn’t count. Even with all this Procrustean work, studies still estimated that each breast or colon cancer still required about 13 driver mutations.
That’s better than the 50–80 mutations but a lot worse than the two- or three-hit theories of the 1990s.
But the mutations within tumours were uneven, too. In a study of 210 human cancers, 20 tumours had between 10 and 75 mutations while a full 73 had none at all! Bloody hell. If mutations caused cancer, how could 35% of the disease not have a single mutation?
Researchers identified a full 120 different driver mutations. Bloody hell. Over half of the tumours had completely different driver mutations.
But there was another insurmountable problem. If genetic mutations caused cancer, then normal tissues should not have these mutations. But they did. Lots of normal non-cancerous cells had the same mutations as cancer cells.
A detailed analysis of 31,717 cancer cases comparing to cancer-free controls from 13 genome-wide association studies came to a surprising conclusion. “The vast majority, if not all, of aberrations that were observed in the cancer-affected cohort were also seen in the cancer-free subjects, although at lower frequency.”
There were more genetic problems in the cancer patients, for sure but not by a lot. The odd ratio was only 1.25. Lots and lots of people had the same mutations in their genes but were not developing cancer. This is a real problem.
In other words, yes, cancers have mutations. But no, these mutations were not the cause. Kind of like saying that great basketball players all have two hands and two feet. Without exception. Therefore, having two hands and two feet makes you a great basketball player. That’s a problem if lots of people also have two hands and two feet and suck at basketball.
Yes, cancers have lots of mutations. But so do lots of non-cancerous cells.
The other major problem is that the somatic mutation theory focuses primarily on the original mass of the tumour. But this is not the part of cancer that kills. It really only kills when it spreads — the metastasis.
The facts fall far, far outside the “cancer as a collection of random genetic mutations” narrative. We’ve tortured the facts as far as possible to fit the predetermined story.
It’s time to leave the Procrustean Bed.
- Dr Jason Fungs founded and runs the Intensive Dietary Management Program. The program provides the education, guidance, support and structure necessary for successful weight loss and type 2 diabetes reversal.
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