The ramblings of an Eternal Student of Life
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Saturday, October 27, 2018
Health / Nutrition ... Science ...

I became interested recently in the biology and pathology of cancer, the detailed medical explanations of what cancer is and how it occurs, after reading a very thought-provoking article in Sci Am based on a Yale study done in 2016. The article discusses a new conception of how cancer emerges in the body and why it remains resistant to the therapies that we throw at it. This “new conception” is based on the biological theory of evolution. I followed up by checking out two other recent articles that relate to this “new view” of cancer, and I hope to read more in the near future.

I am not a scientist nor a medical professional, and my knowledge of biology and evolution and genetics are very limited. It appears to me however that applying the paradigms of bio-evolution to cancer, and to its ability to rapidly adapt to all that we confront it with, is extremely significant. If it can also extend this to the long-term process of how cancer evolves from healthy cells over time in response to repeated environmental and internal “insults” (including challenges from the body’s immune system), then I would call it “revolutionary”. Evolution leading to revolution!

Here’s a quick summary of what I think this revolution is about. Once upon a time, it was thought that cancer was mainly about rapid cell division and undesirable fast multiplication of mutant body cells. The role of DNA mutation was to trigger the division / multiplication process, to “light the fuse”. The mutation was generally seen as caused or triggered by some external poison, e.g. smoke or chemicals or air pollution, or maybe a virus.

Later on it was realized that it takes a string of successive mutations to trigger cancer; but the mutation process was still the tail, not the dog. It was just that the state of rapid uncontrolled growth needed 4 or 5 “switches” to be flipped by a series of DNA modifications, not just one. Some of these mutations must shut down the genetic control devices that our cells contain to suppress rapid growth or kill the cell when it gets too old or otherwise goes bad.

But now, mutation itself seems much more prominent in the cancer process; it continues to happen, faster and faster as the cells divide and grow more rapidly as they become cancerous. Mutation isn’t just the trigger, it is part of the overall process. It helps cancer survive the defenses of both the body and of modern medicine, it makes cancer awfully tough and deadly.

So you might ask, why? It seems as if cancer cells are acting like bacteria. But cells in the human body should be very different from one-celled things like bacteria. It’s like the difference between a musician on stage playing solo, and an orchestra. Or maybe a small jazz trio. The one guy or the trio can innovate and deviate during a song, can be spontaneous, can “mutate” a tune as it is played; but an orchestra has to stick to a plan. Mutation on the part of one violin player or trumpet player is very bad, it can send the music into disarray. You don’t get hired into an orchestra if you are prone to “mutation”.

So why do human cellular orchestra members start behaving like solo artists sometimes? Why do human cells need control devices to keep them from running amok, devices that are shut down by the cancer mutation process? Is it that they were originally solo artists, and something of that style of music gets triggered in them under certain conditions, even though they now play in an orchestra?

This is a “wild-assed guess” on my part — that some underlying trace of the behavior mechanisms of ancient one-celled creatures gets triggered in the human cellular orchestra under certain conditions. Just as one rouge musician in an orchestra can ruin its performance, a few cells gone wrong in a certain way can be deadly.

Oh, here are links to the three articles I am basing my thoughts here on —

A synopsis of the Sci Am article on “the cancer tree” paradigm, from Dr. Jeffrey Townsend. Here is an informative graphic from Dr. Townsend that summarizes the “cancer tree” idea.

A recent web site article by a grad student named Alyssa Shepard regarding the failure to find dietary or pharmaceutical means to prevent cancer.

And a 2016 article on the Sci Am web site discussing the evolutionary paradigm for cancer in the context of therapies, by Cassandra Willyard.

And a footnote — the evolutionary approach to cancer is not really all that new, as it was proposed by Dr. Peter Nowell in 1976, in his article entitled “Clonal Evolution of Tumor Cell Populations“.

This “new paradigm” of cancer is rather scary for an aging human like myself, given that it shows cancer to be tougher than we thought, and at the moment we know of no sure-fire way to prevent it. And yet, this new approach may be very hopeful in the long term. It certainly helps the reader to appreciate why cancer continues to be so difficult for the medical profession to reliably deal with, despite all of the “miracles” that we hear about.

These articles lead me to wonder whether the new “evolutionary” approach to cancer has meaningful parallels with the modern problem of microbial antibiotic resistance. I’m out on thin ice here given my lack of expertise in cell biology and genetics, but I wonder if antibiotics have a problem with microbes similar in a way to the human body’s vulnerability to cancer. Antibiotics become ineffective over time because of the rapid mutation and division capabilities of the one-celled creatures that they try to kill. It seems to me as though the process by which dangerous microbes mutate and thus become increasingly resistant to antibiotics is comparable to what has recently been discovered about cancer’s ability to respond to therapy by “mutating around it”. E.g., a chemotherapy may work for a while, but eventually the cancer comes back because one or two cancer cells survived by mutating in the right way to resistant to the drug.

To take it even further, I wonder if the development of antibiotic resistance may have parallels with cancer genesis itself, thus helping to explain the unreliability of preventative measures (avoiding things like smoking certainly do help to prevent cancer, but eating more fruits and veggies unfortunately don’t, for the most part).

OK, I’m gonna drill down now and go into some detail over how I imagine this might work. I’d love it if a real expert in the field of cancer research were to come across this and let me know if what I say here might be feasible, or if I’m totally out in left field, given my lack of understanding of human cellular biology and pathology. I sense that the odds are long that what I say here have any validity and any value to the medical world in its struggle to better understand and and more effectively treat cancer. But hey, why not take a shot, there’s nothing to lose.

OK, so the evolutionary cancer paradigm focuses in on what the DNA of our cells are doing (and possibly also the epigenetic processes) and what they are experiencing when they start becoming cancerous. We need to get a grip on how a chance-driven selection processes works over long time frames at the human cell level. My guess is that there is some sort of common mechanism in the genetic machinery of both human cells and microbes, such that when they encounter threatening environments, they increase their propensity towards genetic mutation and rapid division.

My general “gut sense” here is that when a single cell such as a bacteria or fungus exists in a supportive environment, it is more likely to “leave well enough alone” in terms of preserving the integrity and stability of its DNA and its reproduction rate. But when a challenge is encountered (either an external poison or an internal attack by immune cells), could it be that a mechanism is triggered in a human cell that increases its likelihood of dividing and mutating its DNA? (That mechanism might be genetic or epigenetic or both, I would guess.)

I am imagining that when either a human cell or a microbe is threatened, it triggers a generational trial and error process that will usually fail, but if done in large enough quantities, a new strain resistant to the threat may evolve and thrive. And could it be that cancer is a situation where the fast mutation/fast division mechanism gets amplified with repeated insults, and finally reaches a tipping-point level where it becomes uncontrollable by the body, even though the triggering environmental threats were only intermittent and variable.

I am further imagining here that somehow, human cells have genetic and/or epigenetic mechanisms that have been passed down over many eons from very early one-celled creatures. (OR that later on, we or an ancestor species accidentally adopted such gene sections from microbes via “gene jumping”, transposons.) Since I am deep in SWAG-land, I will propose that this “coding” is lurking somewhere in the “junk DNA”, the seemingly silent portions of our genes that don’t appear to have obvious and known uses in creating proteins and regulating our body systems.

So I am imagining that a survival mechanism that evolved for one-celled creatures and provided fitness for them is still hidden in our genes, and asserts itself over time from multiple cell challenges and insults. From the luck of the draw over large numbers, a few cells go off on an evolution track in response to these intermittent insults, and survive to be able to quickly divide and mutate, having gained fitness against many chemo-insults and immune system challenges. Eventually, an insult pushes the cells past some “tipping point”(usually later in life, after many adapting to many past insults), such that they go wild; they start dividing rapidly, and even worse, have become able to travel through the body mostly immune from our own self-defenses.

At present, there is a lot of research going on that focuses on mole rats and other animals that don’t get cancer. If certain animals, which are a lot closer to humans than to early one-cell life, don’t manifest the “lurking ancient DNA” that I postulate, that would say that I am wrong; that cancer is a later, self-evolving mechanism, mostly specific to the species.

HOWEVER, the grad student article that I cite above contains hints that perhaps these creatures have been lucky enough to have evolved very robust counter-measures that could hypothetically control the “ancient process” that I imagine. If future research can “knock out” the genetic cancer defenses in these creatures so as to make them subject to cancer, this would would help to answer my question! If they can be induced to have cancer, then perhaps the “ancient mechanism” that I imagine might be there for these animals too — as you would expect.

Next, please allow me to summarize my SWAG theory — it has two components. The first component imagines that cells, both ancient and in higher animals including humans, increase their mutation rates in response to challenges. Google has referred me to some articles that appear from a layman’s perspective to support that notion. E.g., here and here.

The second component is that cells would do better to increase their division and reproduction rate in the face of an insult, as to support the mutation process, as to throw out as many possible variations of itself against the challenge in the “hope” that one variation will survive and adapt to the challenge. However, studies show that the basic observed response of simple cell organisms that are threatened (e.g. by a salty liquid) is to take longer to divide. Here’s an article on that.

So that would go against my idea. But it is interesting that the article I cite also finds that the standard deviation of division times increases as average division time increases in response to environmental stress (such that the coefficient of variation stays roughly fixed as the stress increases). Could it be that the handful of cells that are represented in the left tail of the time distribution are the most likely to survive the stress? And that if this process repeats itself, eventually a cell evolves that divides more and more quickly in the absence of stress? Could that be the road to cancer?

And finally, one more attempt to bolster my crazy idea — I read a study indicating that there are extra-genetic memory mechanisms acting amidst populations of one-cell beings. Could this bolster an adaptation process responding to repeated stresses?

You might ask, just why am I imaging all of this, why am I spending precious hours pondering all of this as my life grows shorter and shorter? Because, if it were true and if science could discover it and learn to manipulate it (and hopefully interfere with it), then we would have an extremely powerful weapon against both cancer metastasis and the antibiotic resistance crisis. And both things scare me, admittedly (I am age 65 and have already had biopsies and MRI scans looking for cancer; and some years ago, my mother contracted MRSA while hospitalized).

Furthermore, it would be a psychological relief to many if cancer could finally be explained simply — i.e., that bacteria-like things are programmed to survive just like us, and they came up with ways to survive when threatened. Today those survival mechanisms, with enough time, can foil our attempts to use drugs to kill the bugs that threaten us, i.e. anti-biotic resistance. And because we evolved from bacterial-like things many, many eons ago (or adopted some of their genes at some point), this mechanism is lurking in our own DNA.

By luck of the draw, with enough draws, our cells can thus go out of control (thus explaining why cancer is largely an old-age disease), creating variations of our own body that adapt to and evade whatever we throw at it to kill it. Yes, like a grade B monster movie. This mechanism is good for bacteria, but no good for us. None the less, it tagged along throughout evolutionary history, and was not selected out by evolution because by the time it would kick-in, most animals would have already died from environmental factors or infections. Only humans overcame the environmental and infection problems (although the resistance problem is threatening us anew with infection), and thus learned to live longer; and now the bacteria-survival process does have time to affect us. As cancer.

And to complete my fairy-tale . . . I hope that one day, doctors and medical scientists can say . . . “but now medical science is on to this, and is honing in on the ancient survival mechanisms that were left in us by early microbes. We hope that we will soon shut those mechanisms down so as to PREVENT cancer, or at least slow them up enough so that our cancer defenses will work 99% of the time. Although that is not going to be easy, as it does not involve just one “switch” or section of the DNA; quite a number of different cell mechanisms are involved.

Just another old man’s dream.

PS — 10-19-18 — An article in The Atlantic sez that a researcher has found a gene and protein mechanism in bacteria that causes faster mutation when the bacteria experiences a threatening environment (e.g., an antibiotic that it doesn’t yet have resistance to). This discovery might allow an adjuvant therapy to be developed that would help maintain the effectiveness of antibiotics, discourage the resistance process in the bacteria being targeted.

What’s more — this protein and its mediating gene (called “Mfd”) might also serve to protect the mutated DNA from damage or further mutation from the antibiotic after the mutation on division. That means that if the mutation gets lucky and does provide the bacteria with resistance to an antibiotic that is threatening it, the new resistant version of the DNA won’t get messed up by the antibiotic before the hosting bacteria cell can split and reproduce itself, thus starting the process by which an antibiotic becomes worthless. Another gene and protein works with Mfd to carry this out (called “RecBC”). That’s what you would expect — it’s probably not just one gene, the process of developing resistance probably involves a network of interacting genes.

SO — can the scientists find an equivalent to this gene in humans, one that drives the mutation process when human cells are threatened by poisons or immune cell attacks or whatnot? Is that the process behind cancer?

◊   posted by Jim G @ 11:52 pm      

  1. Jim, First, I think I need to mention how little I know about the chemistry involved in the topic re the latest thinking on cancer; I might also mention that “epigenetics” is not a term that I think I understand with a simple explanation from an article on Google. On a less important note, I am not sure what “SWAG” refers to either; but according to the “urban dictionary” online it seems to have a meaning of “trending”; but I have to admit that I am not sure even what “trending” means. I have a bad case of what I am calling “OLS” (Old Lady Syndrome). The best I can do with the meaning of “trending” is that it refers to what people are interested in right now; wait a day or two and it is no longer “trending”. Be that as it may, I am not interested in fussing about the meaning of “new words” until they get used enuf to be accepted words that have actual meaning to young people. Perhaps I’m avoiding the issue here cuz I’m’ not sure where to start on this most interesting subject that is so new to me.
    I have always tho’t that our way of treating cancer was, to say the least, not the best—basically, poisoning a person to where he/she almost dies to kill the cancer, hopefully; then bringing them back to a life without cancer. The whole thing makes me wonder if any of it would actually be worth it. It seems FINALLY, while they still do not have a better way of treating cancer, they have a better concept of how it’s caused which will change how cancer is treated. If one knows how it’s caused, then it may be possible to find a sensible way to treat it. Thank God!
    The idea that the virus(es) that cause various types of cancer lurk in the unused DNA and are part of the original evolution of the human being from one-celled animals) makes a lot of sense to me.
    It also seems that this research has been around longer than one might think; I find myself wondering why this has not become more common information.
    The idea makes wonderful sense to me in so many ways that it seems “right”.
    I also like very much your “gut sense” thinking as I tend to do a lot of the same kind of thinking; I think science could stand a lot more “gut thinking” than it usually will tolerate.
    I find your explanation very understandable. In addition I find it most interesting as I have been one of those who has needed treatment for cancer and who also has needed treatment for a medical problem that is a kind of “hanger-on” to other medical problems. When I had it a couple of years ago, I failed all except the last antibiotic that finally “worked”. Your post gives an explanation of what might be going on in both (different) situations.
    I find myself having a better understanding of what I’ve occasionally read here and there that “someday” a shot similar to those given to avoid the flu may be the treatment for cancer. That is a WOW! And even more, that WOW makes so much sense it likely is right on the track of a cure for cancer.
    I tho’t I might have some questions or even did have some questions until, as I read your post over more and more, I realized that I do not know enough about the chemistry involved to ask a sensible question. I think I do, however, know enough about what you are explaining (and the scientists who are on the forefront of this work are doing) to understand the general idea; and having had the experience of having had cancer and having “failed” too many antibiotics in a certain important case to understand the underlying concept of what you are explaining. If nothing else, I am so glad you have brought to my attention a topic I had no clue existed. Whether you are doing strictly scientific thinking or “gut thinking”, who cares? I tend to prefer the “gut thinking”; there’s something about it that always makes more sense to me. Thank you for your fine explanation of it all, even tho I will probably never get to where I understand the needed knowledge to get a real understanding of the topic. MCS

    Comment by Mary S. — November 2, 2018 @ 1:51 pm

  2. P.S.: On a tangential tho’t: I do see one “catch” in the whole business of living longer, who knows to 100 years or maybe even 150. It does seem to me that the “younger” people of today seem to eagerly grab on to the concept of living a very long life, but they do not consider the many other things in addition to cancer that can go wrong, making life a difficult, “who wants to live like this” type of life past a certain age. I can see for young people who develop some type of cancer way too early in their lives, it would be important to find a way to a kind of “easy” cure for cancer, allowing younger people to live much longer lives. I have a sister who lived 55 additional years due to the discovery of penicillin in the 1940s. Without that she would have died as a child. Fifty plus years is probably a really good thing to have.
    I can also see that making the later years of a person’s life better spent can also be a worthwhile thing. But in a lot of people many things gradually go wrong, accumulating and making the 70s, 80s, 90s in their lives basically spent visiting doctors. As one becomes older too, the relational aspect of life becomes more difficult to deal with, consuming energy one does not have, making life much more difficult to live.
    So while I can see the value in finding a simple vaccine to “cure” cancer, there are other, unrelated aspects of life that may make living much longer lives more difficult than initially considered. But who would readily give up another 10 years of life. It does seem there are plenty of people who readily give such years up at an early age by causing their own deaths. The question then becomes what would make a person want to die early in life? Perhaps a discovery for a cancer cure will bring up many other considerations that one does not initially consider. MCS

    Comment by Mary S. — November 2, 2018 @ 2:30 pm

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