By Jerome Burne
Here are some heretical thoughts about the war against cancer.
“It’s unwinnable. We not going to cure it and we don’t need to.”
“Everyone thinks being diagnosed with cancer is a calamity. It’s not necessarily the case. We can transform cancer from a dreaded killer to something we can live with.”
“Cancer is rather like ageing; we don’t want to beat it or fight it but manage it.”
“Cancer is not disease, it’s a condition.”
What makes them heretical is that the conventional view believes that cancer is the result of random mutations that create rogue cells, which grow fast and have to be fought aggressively with surgery, radiation and drugs.
But the heretical thoughts are not the musings of an irresponsible alternative practitioner but extracts from a talk given by an internationally acclaimed physicist last year who specialises in cosmology. The video can be found on the New Scientist website. His radical new theory about what cancer is and how we might be able to tame it rather than beat it, come from the heart of the cancer establishment.
Four years ago Professor Paul Davies, now Principal Investigator at Arizona State University’s Center for Convergence of Physical Science and Cancer Biology, was asked by the American National Institutes of Health to take a look at cancer through the eyes of a physicist whose methods and insights differed markedly from those of cancer biologists.
Cancer treatment and research is failing
His commission was to come up with fresh insights. The Institutes acknowledged the unimpressive survival rates from the current approach, identifying mutating cancer gene and targeting them with more and more drugs – despite the billions spent on research.
Davies estimate of the benefit of these drugs is surprisingly small. ‘For many cancers, once it has metastasised (spread),’ he says in the lecture ‘drug treatment produces an average increase in life-span of just a few weeks compared with forty years ago.’
So what does he think is going wrong? If you have read my previous post about the pioneering investigations into what drives cancer by Professor Mina Bissell, Distinguished Scientist with Berkeley Lab’s Life Sciences Division at the University of California and an authority on breast cancer, then you will have an idea of what Davies is talking about. It can roughly be summed up with the phrase: ‘It’s the environment, stupid’.
The fact that two respected academics, both known for thinking outside the box, have mounted serious challenges to the assumptions that have dominated cancer for decades should give pause for thought to those who insist that the standard treatment is the only way to go.
Drugs aimed at the wrong targets
The reason for the poor improvement in survival rates is, Davies suggests, because oncologists have been thinking about the problem in the wrong way. Relying exclusively on drugs once a cancer has spread means that sooner than later the new tumour will build up resistance and the drug will stop working.
Instead, he concludes, cancer treatments need to make use of a natural process called epigenetics. It is going on all the time. It is the way that the body turns genes on and off as and when it needs them.
The old idea that genes were unchanging instructions for making proteins is long gone. Instead we now know a huge range of things – the chemicals found in certain fruits and vegetables, cutting back on your calories, putting on a lot of weight, stress, exercise – that can all have an effect on gene activity, including the ones involved in growing and spreading a tumour.
Professor Bissell has run studies showing that the micro-environment around a tumour, what she calls the “extracellular matrix”, is in constant communication with the DNA in the cancer cells and can influence them. Implanting cancer cells into healthy tissues in animals, for instance, can turn the cancer genes off and return the cells to a healthy state, even though their DNA still contains the mutated oncogenes.
Gene mutations aren’t the whole story
Bissell and Davies both hit on the idea of looking for a better way of controlling cancer because they became increasingly disenchanted with the conventional view that cancer is caused by random mutations in otherwise healthy cells.
Davies identifies two problems with this.
The first is that cells with mutations in genes linked with cancer should be very inefficient – most mutations don’t make cells act in a more effective way – yet cancer cells have a remarkable set of abilities. Quite apart from rapid growth, they can travel round the body, find new locations to develop, plug into a local blood supply and even maintain communication with the original tumour.
The other way, Davies claims, that the current model doesn’t fit with reality is that if every tumour grew from a random mutation in a single cell in an individual body, you would expect tumours in different people to be very different and to behave in very different ways. But in fact all tumours have similar abilities and patterns of behaviour.
Davies big idea is that we all have what might be called a “cancer program” in our DNA waiting to start running, just as we have ones to respond to stress or to deal with starvation. That’s why cancer cells have such an impressive toolbox and behave in a similar ways. The cancer program is running on millions of years of evolutionary development. (More details.)
Creating a cancer-unfavourable environment is key
It means that cancer is not just about mutated genes; it is running on perfectly good genes, which have been triggered inappropriately. The way he expresses it is that cancer is a default mode, or a reversion to an ancestral phenotype, rather like Safe Mode on a computer, in response to a stress or insult. In this mode, cells run on their core functionality, which is very robust as it has billions of years of evolution behind it. This reversion can happen in response to a variety of factors including toxins, radiation and inflammation.
If he’s right, and he describes various ways his theory can be tested, it means that trying to “kill” cancer is very often doomed to failure. However the up side of this is that getting a better understanding the local or epigenetic factors that can either encourage cancer growth or switch it back in a healthy direction – or merely contain it in a quiescent state – makes a lot of sense.
It also brings into sharp focus how best to tame cancer rather than trying to defeat it. This involves exploiting the difference between a cancerous cell and a healthy one. So the challenge becomes – what can we do to make conditions inside and outside cancer cells as unfriendly as possible?
This is quite different to the current approach which frequently combines the chemical blunderbuss of chemotherapy that degrades healthy and cancerous cells alike and the sniper rifle of newer drugs aimed at specific genetic changes, which means treatment is always in a race with resistance.
Mainstream ignores real cancer drivers
The differences Davies has identified that are unfavourable for cancer – largely ignored by the cancer mainstream –include high levels of oxygen, low levels of glucose and a pH balance that is more alkaline than acid. These are all things that can easily be maintained by the life-style changes already recommended by clinicians following a non-drug approach to cancer.
According to Davies the opposite conditions that favour cancer – low oxygen, a regular supply of large amounts of glucose and acid production – are all the result of the way cancer cells produce energy. They are the conditions found in our distant evolutionary past when the cancer causing program first emerged and there wasn’t much oxygen around.
This was the time – about 1 to1.5 billion years ago – when life made the transition from single to multi-celled organisms. As cancer represents a breakdown in the regulatory mechanisms that ensure that individual cells conform to the organism’s overall agenda, it makes sense to trace the evolutionary roots of cancer back to that time, or even before.
Both he and Bissell drew inspiration from the first scientist properly to describe this difference in the 1920’s – the Nobel prize-winning German biochemist Otto Warburg . Despite being partly Jewish he survived the Nazi regime thanks to Hitler’s fear of cancer and his hope that Warburg would come up with a cure.
Cancers love glucose, hate oxygen
Davies sums up the way their cruder energy system makes cancer cells vulnerable with the phrase: ‘Cancers love glucose and hate oxygen.’ The low oxygen means that they can’t make energy the way healthy cells do – with the tiny power plants called mitochondria found in every cell that depend on generous amounts of oxygen and a modified form of glucose.
Tumours rely on a more wasteful method that uses glucose directly. The benefit as far as the cancer is concerned is that it is faster, which is good if you only care about growth. The waste product of his system is lactic acid, which is what shifts cancers in an acid direction.
Davies (who is a physicist and not a physician) has little to say about the specifics of creating a cancer-hostile environment but one way of cutting down the glucose supply that has been getting a lot of attention recently is the ketogenic diet – a sort of modified Atkins – which involves having no more than about 25 grams of carbs a day and instead eating a lot of fat. (See “Starving cancer: why it makes sense.“)
What we can learn from the foetus
As well as degrading the cancer’s glucose supplies, the diet also generates an alternative source of energy known as ketones. Healthy cells in the brain and muscles happily burn ketones in their mitochondria but cancer cells can’t use them because their mitochondria aren’t working properly. (Read more…)
Other dietary changes can push the body in an alkaline direction while cancer’s dislike of oxygen can be exploited by putting patients in a hyperbaric chamber that increases the amount of oxygen that gets into cells.
One obvious question is why on earth should we have evolved with a primitive ready-to-go cancer program lurking in our genes? Why wasn’t it weeded out by natural selection? Surely people without this cancer booby trap would have an advantage? Davies explanation is to point to the similarities between cancer and the growth of a foetus in the womb, which in a loose sense recapitulates the body plans of ancient organisms.
As it happens, the link between cancer and embryo development has been known to cancer biologists for decades, but is largely ignored. For example, many genes that are active in embryos are known to be re-awakened in cancer. Furthermore, embryos start out in a low-oxygen environment too, and accumulate biomass very rapidly. They also undergo a type of “organized metastasis” when cells that are differentiating into specific organ types perambulate around the foetus to make a home in their designated locations. These absolutely vital functions can’t be bred out. ‘Jettisoning them, says Davies ‘would fatally compromise the embryo’s development.’
Exploit the difference between healthy cells and cancer cells
But what we can do when the “foetus program” is triggered inappropriately later on, is to create a cancer unfriendly environment?This makes the most sense, Davies believes, as a way to cut the risks of the cancer spreading (metastasising). ‘This is still a pretty mysterious process,’ he says. ‘Most of cancer cells that do set off on a metastasising journey never make it and those that do may lie dormant for years.
‘Lots of people die with cancer that hasn’t affected them. If the period of dormancy could be extended by a factor of five, many breast, colon and prostate cancers would cease to be a health issue.’
Of course more research is needed to establish just how effective these epigenetic and micro-environment changes could be and how best to combine them with more conventional approaches. Investigating them makes sense even if Davies theory of cancer as primitive throwback program turns out to be wrong.
Bringing a physicist’s eye to bear on cancer has highlighted important difference between tumour cells and healthy ones and thrown up possibilities for deliberately exploiting them.
Jerome Burne is the editor of HealthInsightUK. He is an award-winning journalist who has been specialising in medicine and health for the last 10 years and now works mainly for the Daily Mail. His most recent book “10 Secrets of Healthy Ageing” was written with nutritionist Patrick Holford. He blogs at “Body of Evidence” – jeromeburne.com.