Convergent Evolution and Cancer – Cancer 9

The concept of evolution is very useful as it applies to cancer, because it forms a paradigm of understanding that simple genetics cannot match. Charles Darwin, studying animals in the idyllic Galapagos island formulated the theory of evolution by natural selection, which was revolutionary at the time he published it in his book On the Origin of Species (1859). According to legend, he had noticed that the shape and size of the beak of a finch varied according to the food source.

For example, long, pointy beaks were great for eating fruit, whereas the shorter thicker beaks were good for eating seeds off the ground. He reasoned that this could not simply be a coincidence. Instead, he postulated that there was a process of natural selection going on here.

Just as with humans, there are those who are shorter or taller, muscular or lean, fatter or thinner, blue or brown eyes. Within a population of birds, there are those with longer and shorter beaks, and thinner and thicker beaks. If the main food source is fruit, then those with longer pointier beaks had a survival  advantage and would reproduce more often. Over time, most of the birds would have long pointy beaks. The opposite happens if the main food source is seeds. In humans, we see that people in northern Europe tend to have very fair skin, which is better adapted to the weak sunlight compared to the dark skin of native Africans.

While ‘genetic mutations’ is the proximate cause of this natural selection, the environment is ultimately what guides the mutation. What is important is not the specific genetic mutation that led to long pointy beaks, but the environmental condition that favored the selection of long pointy beaks. There are many different mutations that may cause the same long pointy beak, but cataloging these various mutations does not lead to understanding of why these beaks developed. It was not a random collection of mutations that happened to create the long pointy beak.

This story of Darwin and the finches (which may have been tangers) may or may not be true, but it led him to look more closely at an artificial model of a similar phenomenon. Instead of natural selection, he used artificial selection.

Pigeons (actually Rock Doves) were domesticated many thousands of years ago, but in the 1800s there were pigeon fanciers that would breed these birds to look a certain way.

If a breeder wanted a very white pigeon, he would breed together mostly pigeons of very light coloration, and eventually, he would get a white pigeon. If he wanted one with huge feathers around the head, he would breed together birds with similar features to those he wished and eventually, it would result.

This form of artificial selection has been going on since the dawn on humanity. If you wanted cows that gave a lot of milk, you would breed together the most prolific milk producing cows over and over over many generations. Eventually, you got a Holstein cow, with its familiar black and white pattern. If you wanted tasty meat (with a lot of marbling) you eventually got Angus beef.

In this case, there was not natural selection, but artificial, man-made selection for one or another trait of beef or bird. It was no ‘random mutation’ that created the Holstein cow, but selective pressure based upon milk production. The ‘mutations’ that produced more and more milk were bred together, and the others became beef stew.

What is important, however, is not that different species result from genetic mutations. This is a given. What is important is what is driving the mutation towards the end result. If we select those with more milk production, we drive mutations that lend themselves to milk production. If you have similar environments, you may end up with similar mutations.

This concept in biology is known as convergent evolution. Two completely different species which develop in similar environments may eventually look like twins. The classic example are between species in Australia and North America. The mammals in North America are genetically unrelated to the marsupials in Australia, but look how closely they resemble each other. In both cases, flying squirrels developed completely independently. Australia is an island, completely separated from North American, but similar environments led to similar selective pressures and the development of similar features. So there are marsupial counterparts to moles, wolves, anteaters etc.

Once again, it is the selective pressure that drives the mutations that survive best. It would be completely preposterous to say that flying squirrels develop from a completely random 200 mutations in the genes of a squirrel and hey, by coincidence the exact same thing happened in Australia. The key is to look at the selection pressure. Living among the tree canopy, there is a survival advantage for squirrels to develop the ability to glide. Thus, in both North America and Australia, you see similar flying squirrels. However, the specific genetic mutation that caused these changes are completely different. Knowing the environmental pressure that drove selection of these mutations is far more important.

Now let’s go back to the cancer. We know that all cancers share similar features, the so-called Hallmarks of Cancer (unregulated growth, angiogenesis etc). While you may have one breast cancer with one set of mutations, you have a completely different set of mutations that looks exactly the same as the first. Clearly this is a case of convergent mutation. If mutations were truly random, then one set of mutations may have unlimited growth (cancer) where the next may glow in the dark. There is nothing random about cancer’s mutations because they all develop the same features.

So the cogent question is not what particular mutations are underlying cancer, down to the minute pathway details of the particular oncogene. This is the downfall of cancer research. Everybody is focused on the nitty gritty of the particular gene. All research focuses on detecting the genetic abnormality without understand what is selecting those mutations. The 45 year war on cancer has become nothing but a giant exercise in cataloging the millions of possible ways that genes may mutate.

The most famous cancer related gene p53, was discovered in 1979.  There have been 65,000 scientific papers written on this gene alone. At an conservative cost of $100,000 per paper (this is likely way, way too low) this research effort myopically focused on random gene mutations has cost $6.5 billion. Holy Shittake Mushrooms. That billion with a B. 75 million people have p53 related cancers since the time of p53’s discovery. Yet despite this enormous cost, both in dollars and human suffering has produced a grand total of zero FDA approved treatments based on this expensive knowledge. Shut the front door. I could heap more scorn onto the Somatic Mutation Theory, but I’ll spare you. We are losing the forest for the trees. We’re looking so closely at the specific genetic mutations, we can’t look at why these genes are mutating to produce cancer. Look, tree. Look, another tree. Look, another tree. I don’t understand what this ‘forest’ thing they’re always talking about.

The key is to look at what actually is driving those mutations, not the mutations themselves. What is causing cancer to become, well, cancer? This is really the same question as looking at the proximate versus the ultimate cause. These cancer cells are being selected to survive, when in truth, they should be dead. It cannot be random, because multiple different mutations converge upon the same phenotype. That is  – all cancers look alike on the surface, but genetically, they are all different, just as the marsupial flying squirrel is completely genetically different from the mammalian one, but look exactly the same.

Looking at cancer through an evolutionary lens is perhaps the most helpful way of perceiving it. Cancer as unbridled growth was Cancer Paradigm 1.0. This lasted up to about the 1960 or 1970s, when an explosion of knowledge in molecular biology forced the view of cancer to a genetic one. Cancer as collection of random mutations causing unbridled growth was Cancer Paradigm 2.0. This lasted from the 1970s to approximately 2010s although there are still some diehards who believe it today. The Cancer Genome Atlas was the final bloody knife in the bowels of this somatic mutation theory, tearing it painfully and irrevocably apart until no serious scientist could use it.

Now, with an evolutionary lens, we peel back the onion of truth one more layer to see what is driving those mutations. That is Cancer Paradigm 3.0. Something is driving the mutations that are driving the unbridled growth of cancer. The answer to to Darwin’s question of ‘why do many birds have long pointy beaks’ is not ‘random genetic mutations’. The answer to Cancer’s question of ‘Why do so many cancers share similar traits’ is also not ‘random genetic mutations’. Something is selecting these cells for survival.  That something increasing looks to be mitochondrial damage and metabolic health.

 

Start here with Cancer Part 1

Continue to Cancer Part 9 – Nutrition and Cancer

2018-04-25T16:56:40+00:0020 Comments

About the Author:

Dr. Fung is a Toronto based kidney specialist, having graduated from the University of Toronto and finishing his medical specialty at the University of California, Los Angeles in 2001. He is the author of the bestsellers ‘The Obesity Code’ and ‘The Complete Guide to Fasting’. He has pioneered the use of therapeutic fasting for weight loss and type 2 diabetes reversal in his IDM clinic.

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Amanda K
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Amanda K

From an evolutionary perspective, you are speaking about survival of the fittest .Like Dr. Fung said, there is variation in a population (eye color, height,weight, etc). Natural selection of traits occurs from what is already present in the population. For example, when discussing finch beak characteristics, in a year where food is plentiful, beak size and shape are not very important. A finch that has a beak that is not so good at crushing shells to get seeds out is not a big deal because it can find food elsewhere. It still survives and passes on its traits. Natural selection… Read more »

Patrik
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Patrik

Cancer is a defense mechanism the body applies to invasive fungal growth. The microfungus, usually Candida, emits aflatoxin which destroy cell mitochondria thus making the cell cancerous. The tumor isolate the fungus and the cancer cells ferment to deprive the fungus of its nutrition. If the amount of glucose driving food and over all calories are reduced (caloric restricted ketogenic diet), the fungus will usually weaken and the tumour recess. Look into Thomas Seyfrieds research.

sten bjorsell
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sten bjorsell

I agree with J.F. and with the latter half of your comment, as Thomas Seyfried has shown that sugar deprivation reduces tumor growth and PET scans show that sugar stimulates it. The single(?) known common denominator of such damaged mitochondria is continuous lactate formation also in the presence of oxygen, the Warburg effect. Hence we must focus on what cell mutations an environment dominated by elevated lactate can cause. The “cancer event chain” seems to be: Environmental stress -> damaged mitochondria -> constant lactate production -> cell nucleus mutations. The last step enabled, permitted or forced by the new cell… Read more »

Benthamite
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I have pasted on my website a journal article on the role of macrophages in tumors, and how they turn on genes in tumors which make them invasive at http://healthfully.org/rcdm/id1.html Do you have links to articles on tumor as part of the immune system.. The standard view is that anaerobic metabolism avoids apoptosis.

Patrik
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Patrik

First: Thank you both for the thoughtful comments and to Dr Fung for the interesting articles on cancer. I hope it was clear that my post before is just a hypothesis but I think it fits well with Seyfrieds research. All organisms has to defend itself against invasive fungal infection during its entire lifetime and when this mechanism fails, usually post mortem, we immediately start to decompose. Fungus and fungus spores are dormant in all living things ready to take action on the slightest sign of weakness. An apple on the window shelf will soon start to rot. Cancer seems… Read more »

bruce hennessy
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bruce hennessy

This is a wrong turn. Darwin detected adaptation, not evolution. Macro-evolution, that is, one kind of living thing eventually becoming another kind is bunk – there’s no such thing. And please see the poor example of BENEFICIAL selection of genes (birds beaks for improved feeding, flying squirrel for improved survival) versus DELETERIOUS mutations that KILL. No, this is all going in the wrong direction. Rather than considering the evolutionary model, we should be looking at the devolutionary model – something has gone very wrong with the world, not too long after the start of it all. Something has corrupted the… Read more »

cathy weaver
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cathy weaver

I absolutely agree with Bruce’s summary. I also love Dr.Fung and his work.

Elena
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Elena

I absolutely agree on evolutionary theory. No doubt it is going on every moment of every day. However on the cancer theory there could be other variables along with what you have all mentioned. And that is the most recent several hundred years we do most of our living inside and cover our bodies. From my personal studies low sunshine on the torso is to blame for failing autoimmune systems of the body. I suspect if our D scores were increased to what they would have been out under the sun all illnesses, including cancer would fall by 50% (maybe… Read more »

Grant
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Grant

We shouldn’t bother with this dark age creationist think, but I’ll bite anyway. “the marvelous ability for living creatures to ADAPT to their environments is a design feature of VERY GOODNESS.” Please tell me the VERY GOODNESS of the adaptations of intestinal parasite, the hookworm. Yeah, you know, the hookworm that cause infection and pain for up to a 15 years by latching onto your intestine with tiny teeth. Or, how about the VERY GOODNESS of the adaptions Ichneumonidae family of wasp. You know, the wasps inject their larvae into the body of living caterpillars. That’s a VERY GOOD type… Read more »

Roger Bird
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Roger Bird

Please stop being insulting, unless of course you don’t think that you ideas have sufficient merit. I am down-voting because of your insulting and dehumanizing behavior. I thought that your ideas were spot-on, but your conclusion hurt my heart.

bruce hennessy
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bruce hennessy

The “dark ages” you speak of followed AFTER the Light. I don’t speak of the religion of men, the Roman church or any other medieval incantation of truth. Indeed there are “dark ages” throughout history, and always consist of a falling away from the glory of God. Are there BAD adaptations as such you point out? Well, when there has been corruption of the VERY GOODNESS of God’s created order, why wouldn’t there be? I mean we are talking CANCER here, so why would I even need to go to the hookworm or other for proof of badness? The very… Read more »

Richard
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Richard

Grant, Thanks for your post. Although I think that what Dr. Fung relates this to is loss of ancestral dietary practices, such as increased and excessive reliance on carbs/sugars as a human food source and too much insulin being generated as a result of that and near constant eating (snacking), that is the only connection I see to any “historical” concept. The idea for me is to understand what has created this excessive reliance on carb food sources and constant eating paradigm, and how to overcome or resist being a victim of that situation or “reality.”. Trying to turn this… Read more »

John Brown
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Bruce, Sinning is just a label for certain types of behavior. Exercise is a behavior. Eating lots of sugar is a behavior. These behaviors have studies which demonstrate they do have effects. So if you think you’ve identified other behaviors, who are we to say it’s impossible such behaviors don’t affect health? The thing that’s needed, however, is rigorous science to support your claim. If you really think your idea is true, then it should show up in well-designed and rigorous epidemiological studies. Those studies won’t show causation. But correlation is a good start. What you’d see is a statistically… Read more »

bruce hennessy
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bruce hennessy

I hear you John. However sin is first and foremost a condition, not behaviors. I am not saying that we all need to go out and “be good”, and convince others to “be good”. We can’t, it’s impossible. The absolute condition of sin is simply this: rejection of God. It’s saying that you “see”, when in fact you do not see. There are many who “do good”, but their motivation is inherently evil without it being first and foremost about giving glory to our Creator. I understand that that sounds ridiculous and may be annoying because God seems to be… Read more »

John Brown
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Bruce, what you’re describing seems to still be a behavior. I understand you want to couple motivation with it. Motivation is not directly observable, but I’m sure you could come up with something, some kind of survey, that would indirectly measure it. However, even if you didn’t do that, you’d think that if your claim were true, it would show up in populations where more people were likely to exhibit the motivation or mindset you’re talking about. There are studies that have looked at cohorts defined by their religion. For example, there have been studies done that correlate positive health… Read more »

Oscar
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Oscar

This is a cientific blog please… this has nothing to do with realigion point of view wich sometimes they are a valid point but not always as they were created by points of view of humans not nature.

John Brown
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Wow, great post. I guess it shows my ignorance of evolution that I thought it was indeed random mutations with the finches. Loved the subtle humor of the cow graphic and some of the associated one-liners.

Roger Bird
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Roger Bird

It is rare that such a great intellect can be so funny, witty, playful, down to Earth, practical, and still have a wide vision..

Roger Bird
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Roger Bird

Dr. Jason Fung is an intellectual god.

Benthamite
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The problem with the war on cancer is the business model. Following the changes made by Congress in the mid 80s, universities had gone into the business of raising money by licensing findings to pharmaceutical companies. Companies and universities are now searching for drugs, a drug to block a gene which switches on a process such as angiogenesis. They are not trying to find out what in our environment such as chemical pollutants and high fructose diet that has caused the cancer epidemic or why wild animals rarely get cancer. Nor are they concerned with why a tumor has certain… Read more »