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    Cancer’s Inconvenient Truths
    By Rafe Furst | December 29th 2010 09:30 AM | 8 comments | Print | E-mail | Track Comments
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    Rafe Furst holds an M.S. in Computer Science and B.S. in Symbolic Systems, both from Stanford University. He is an entrepreneur, investor and business...

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    Inconvenience #1: Genetics represents < 10% of the risk but most of the science

    • In the Prezi above you will notice a statistic that is corroborated by the New England Journal of Medicine: 90% of cancer risk is from non-genetic factors.
    • One of the most striking pieces of evidence for this is a study done on women who move to the United States from Asia.  In their home country their incidence of breast cancer is quite low.  Once they move to the US their incidence rate shoots up to be identical to that of the surrounding population after just a decade.
    • Yet, most cancer research is focused on genes and genetic pathways.

    Inconvenience #2: There may be no general “best way” to live

    • For the tip of the iceberg, check out the raging debate between the mainly vegan camp and the paleolithic diet camp.  The most outspoken authorities are The China Study crowd and the Weston Price crowd respectively.  
    • One side sites reams of evidence that “we humans” do best on mostly (up to 100%) plant-based diets, and the other side sites equal mountains of evidence that large quantities of animal product (over half of your dietary intake) is required for optimal health.
    • Both sides give compelling evidence, epidemiologically and etiologically.  Both sides have compelling critiques of each other’s methodologies, data and analysis.
    • Both camps commit the ecological fallacy over and over again in their arguments.  In other words, what’s good on average in a population may not be optimal for any individual human in that population.
      • Perhaps this is why some people (like the author of The China Study) seem to thrive on a 100% vegan diet, while others seem to die from it.
    • Whatever the case may be, to take sides in the debate is to miss the point.  Both sides have compelling and credible arguments.  Both have well-respected scientists and peer-reviewed literature that back up their claims.
    • The net effect is that “science” as a whole comes to opposite conclusions on the question of what to eat.
    • And given that “what to eat” represents about half your risk for cancer, how should we feel about asking science to help us determine what we eat?

    Inconvenience #3: Environment and lifestyle are inextricably linked

    • One of the more compelling datapoints in The China Study was a series of studies on the effect of various types of protein (animal or plant) on cancer risk.
      • While the methodology has been called into question by the paleo crowd, the results are startling: When exposed to aflatoxin, rats fed casein (a cow’s milk protein) all developed tumors; when fed plant proteins, the tumors went away.
    • This sort of result has been noticed in cancer research for over a century and is referred to as the “seed vs soil” issue.
      • That is, it’s impossible to say definitively whether an agent is a “carcinogen” (i.e. the seed) without knowing the environment (i.e. the soil) in which the organism exists at the time the agent is present.
    • At the human organism level, we have to ask ourselves: is it the ionizing radiation that causes cancer, or is it the the organism’s diet, cardiovascular health and other biophysical context?
      • On the one hand we recognize that context matters because ionizing radiation is one of the pillars of cancer treatment.
      • On the other hand, when it comes to the basic research, we dismiss results like the aflatoxin studies as being either anomalies or methodologically flawed.

    Inconvenience #4: Darwinian evolution is happening inside your body right now

    • Talks by Dave Agus and Carlo Maley lay out the case well.  The wikipedia entry gives historical context for the science.
    • The biggest inconvenience presented by somatic evolution is what it implies for treatments such as surgery, radiation and the most common forms of chemotherapy.
      • When you kill cells indiscriminately and you don’t get every last “bad” cell, you end up selecting for cancerous populations (i.e. tumors).  This is called therapeutic resistance, and eventually all known drug therapies lose efficacy because of it.
      • In some cases -- perhaps more than we realize -- interventions actually initiate metastasis.  Most patients do not die from primary tumors but rather from metastatic cancer.
      • These treatments are part of the standard protocols, and oncologists who stray from them (or take a nuanced approach) are liable for malpractice.
      • Many of the researchers I’ve interviewed feel that most patients who do survive after these treatments -- especially chemo and radiation -- do so not because of them but in spite of them.
    • Cancer-as-evolution was gleaned in 1914 and has been discussed ever since, but its greater implications have been summarily ignored in both theory and practice. 

    Inconvenience #5: Inheritance is not just about genetics

    • When I learned about evolution in high school I learned about Lamarck’s theory: characteristics that a parent acquires during its lifetime can be inherited by its offspring.
      • The motivating example always given was a giraffe stretching its neck to compete for scrumptious leaves.
      • Lamarckian inheritance was crowded out by Darwinian theory which explains long necks via selective pressure.
      • Once we learned about DNA and the mechanism of genetic transmission, this was the fatal blow for Lamarck.
      • Ever since, Lamarckian inheritance has been used as an example par excellence of bad science.
    • It turns out though that diet, exercise, etc. change the methylation patterns on your DNA, which change how your genes are expressed.
      • And those methylation patterns can get passed on to your offspring.  Studies in both mice and humans show acquired cancer risk is heritable up to three generations.
      • In other words, that cheeseburger you just ate affects your not-yet-conceived children’s risk of cancer.
    • But even if you ignore the methylation, what about the dietary habits you pass on to your kids just by virtue of raising them in your household?
    • Of more immediate cancer concern, the cells in your body express a huge amount of non-genetic diversity as part of their normal functioning: Spencer, et al; Brock&Huang; Sigal et al.
    • This diversity is effectively inherited as cells divide, which means that it is grist for the the somatic evolution mill.  Which means it is a driver for cancer.
    • In other words, even if we somehow were to correct all the genetic mutations in your body, this still may not be enough to stop cancer from happening.

    Inconvenience #6: Cancer is contagious

    • The Tasmanian Devil population is in danger of extinction due to a form of cancer which is transmitted via biting.
    • Human cancers can be transmitted via surgical transplantation.
    • Evolution is clever.  What’s to say that a human cancer won’t emerge that is transmittable via biting or other non-surgical vectors?
      • One thing’s for certain, if this is possible, the interventions we do now to treat cancer actually increase the likelihood of the evolution of contagion (because to selective pressure the treatments create).
    • Perhaps of more practical importance, new studies of social network dynamics are revealing that conditions once thought to be individually determined (like obesity and depression) are socially contagious.
      • That is, we can predict whether you will become obese just by looking at the obesity levels of your friends.
      • Any behavior that is mimicked (e.g. smoking) is by definition socially contagious.
    • And since obesity and smoking are two of the biggest risk factors for cancer, it stands to reason that that cancer is socially contagious as well.

    Inconvenience #7: Cancer is an artifact of modern culture

    • While cancer does exist in nature, it is several orders of magnitude more prevalent in industrialized societies.
    • Up until recently this was always viewed as the price we pay for not dying prematurely of infectious diseases, violence, etc.
    • But several poignant analyses suggests that perhaps it’s more accurate to think of cancer largely as a manifestation of human culture:
      • “Cancer is a modern, man-made disease caused by environmental factors such as pollution and diet” (Prof. Rosalie David)
      • ”I have no doubt in my mind that I know what causes cancer... ‘civilization’” (Thomas Cowan, MD)
      • “Every era casts illness in its own image” (Siddhartha Mukherjee, MD)
    • In other words... What cancer is, how to treat it, and how to live with it are all dependent on what we believe to be true about the disease.
    • Science does not do well with self-fulfilling prophecies, but what these researchers are suggesting is that there may be some degree of choice as to whether we get cancer and/or die of it.

    Inconvenience #8: Sometimes doing nothing is the best treatment

    • The picture is emerging that each of us probably have millions of pre-cancerous tumors growing in us right now.  This is normal.
    • Your body will somehow get rid of 99.99999% of them without any medical intervention at all; even those that are detectable.
    • In some cases, removing a tumor will actually initiate metastasis and kill you very quickly.
    • In other cases tumors are so slow growing that it takes 40 years before they need to be removed.  And then only because they are impeding the function of an organ.
    • A leading oncologist is quoted in the NY Times recently as saying that breast cancer diagnosis amounts to    
      • “a 30-year history of confusion, differences of opinion and under- and overtreatment.... There are studies that show that diagnosing these borderline breast lesions occasionally comes down to the flip of a coin.”

    Inconvenience #9: Sometimes it’s better not to look

    • And because treatment has so little to do with outcomes, there is a huge rift in the world of cancer research and policy on the practice of early detection.
    • The following quote from Wired Magazine’s cover story summarizes the paradox of early detection: 
      • “Some cancers can be too easy to find. About 80 percent of prostate cancers are detected early. Yet most patients survive at least five years even if untreated. The problem: deciding whether medical intervention is necessary.
      • Other cancers are inherently elusive. Pancreatic cancer, for one, betrays almost no symptoms, making diagnosis a matter of pure luck. Only 3 percent of cases are found in the first, most curable stage.
      • The money goes where the cancer is. Some malignancies, notably lung cancer, are mostly detected only in late stages. As a result, that's where most research is directed. Shifting those priorities won't be easy.”
    • As we get better at detecting cancer than treating it, a dangerous gap begins to appear between effective detection and effective actions.
    • The question for you as a patient is: given the current state of the art in early detection and treatment, how much do you want to know what’s going on in your body?
    • And knowing that the cure may be worse than the disease, what would you do if you detected something?

    Inconvenience #10: Sometimes True is False.

    • Up until a few years ago one of the Prevent Cancer Foundation’s Top 7 Prevention Tips was to “always wear sunscreen” when going outdoors.
    • Unfortunately, if everyone followed this advice, we now believe avoiding the sun would cause 10 times the cancer deaths that sunscreen would prevent.  Here’s why:
      • Sunlight is critical for your natural cancer immunity (amongst other things)
      • And while it’s true that UVA radiation from the sun causes genetic damage in the skin, the UVB which also comes from the sun ameliorates the effect of that damage.
      • Sunscreen blocks out both UVA and UVB
      • An important detail that often gets lost is that while sunlight increases your chances of getting certain kinds of skin cancers, sunlight protects against all kinds of cancers.
      • It is currently easier to detect pre-cancerous growths on the skin’s surface  than inside the body.  
      • The ratio of solid cancers to skin cancers is over 10:1.
      • Moreover, the most aggressive forms of skin cancers are those that are not initiated by UVA radiation, and which often are found on parts of the skin not exposed to the sun, such as on the scalp.
      • Bottom line: which is riskier for your health, getting too much sun or not enough?
    • Such advice is highly vetted by a Medical Advisory Board that reads as a “who’s who” of research and oncology.  It represents the current scientific consensus at all times.
    • As a Director of the Prevent Cancer Foundation, it is painful and tragic to think that I may have caused more harm than good with my public health advice.
    • In light of these inconvenient truths, and in light of this graph...

    ...here’s question we must ask ourselves as a society: Is the world better off for having approached cancer as a scientific matter or not?


    Shattering the Illusion

    If you are scratching your head at this point, you’re not alone. I rarely meet cancer researcher who is not more humbled and more baffled by their subject matter the more time they spend studying it.  And it’s not just cancer; we’ve reached the point of marginal returns in understanding our economic systems, the global climate, the geopolitical system, and even fundamental physics.

    Have we reached some fundamental limit to the capacity of the human brain?  After all, it evolved not for curing cancer but for much simpler tasks like acquiring food and avoiding immediate danger.  I would argue though that whatever our inherent limitations, we are limiting ourselves artificially by not questioning the efficacy of our methodologies for organizing thought, explanation and prediction.


    I don’t just mean to suggest that our institutions which practice science are dysfunctional -- which they are -- but more importantly, the scientific method has not evolved at pace with the increasing complexity of the world and thereby is becoming increasingly dysfunctional.


    Comments

    Gerhard Adam
    I don’t just mean to suggest that our institutions which practice science are dysfunctional -- which they are -- but more importantly, the scientific method has not evolved at pace with the increasing complexity of the world and thereby is becoming increasingly dysfunctional.
    How can they possibly function when we've hijacked science for short-term profit and the appearance of technological gain?  We know longer acquire knowledge, we find "solutions", whether they are the right ones or not.  It's little wonder that we constantly run off in hundreds of different directions, since we never take the time to actually learn anything.
    Mundus vult decipi
    There is a man in Montréal, Québec, who made a great discovery about the brain cancer. His name is : Richard Béliveau.

    Also, he is teacher of biochimistry in L'Université du Québec de Montréal and directeur du Laboratoire d'oncologie moléculaire of Sainte-Justine Hospital. He is a proud contributor in a televised show who is devoted to good and healthy fooding. His advices to get more chances to avoid a cancer :
    -Don't smoke.
    -Keep healthy BMI between 19 and 25.
    -At least 30 minutes of exercise every day.
    -Avoid junk food and transformed foods.
    -Eat lot of fruits and vegetable (5 to 7 portions each day).
    ****He used to encourage the mediterranean, the asian foods and home made meals.

    Good, here we are... Docteur Béliveau discovered a perpide who can cross the protective gate of the central nervous system. That barrier block drugs before to reach the brain...

    So now, the finding of Docteur Béliveau's team, will probably become the Trojan Horse who will bring drugs into the central nervous system.

    Docteur Béliveau also works in USA.

    rafefurst
    "So now, the finding of Docteur Béliveau's team, will probably become the Trojan Horse who will bring drugs into the central nervous system."

    So given what we now know about somatic evolution, is this a good thing or a bad thing?
    Rafe Furst http://emergentfool.com
    I don't know, but that is a good question... Thanks for your good article. You made me realize that with beasts like those deseases, si-fi and horror writers didn't and don't have to keep on creating monsters to frighten... all is here, in our world , with those cancers who are not animals nor plants, but they live inside human and animal bodies and are also submitted to laws of natural selection.

    As for the question of «Somatic evolution of cancer», I hope that his treatment is good enough to eradicate brain tumors... if not, THEY ARE COMMMMING BACK stronger than ever !...

    rafefurst
    The problem with typing cancers by body part (e.g. brain cancer, breast cancer, etc) is that this does not honor the evolutionary complexity of the disease.  Thus, if you apply selective pressure (via radiation for instance), you run the risk of turning brain cancer into breast cancer, testicular into brain, etc.  This is known as metastasis. 

    Rafe Furst http://emergentfool.com
    Aitch
    Good article, Rafe

    From hard experience, I concur.....have you been affected directly or a family member?

    To anyone diagnosed with, or with Cancer in the family, I would say research is your best weapon, and determination and positivity, your survival

    Aitch
    Hi Rafe,

    That's a good post! I like most of it but I am not entirely sure I agree with it all. I am definitely not a big fan of all this obsession on the genetics of cancer but (you knew there was a 'but' coming!) even if it were true that non-genetic factors are responsible for (the initiation?) of 90% of cancers the fact is that you still have to understand genetics. Regardless of the initiating event, cancer cells are genetically different from normal soma cells and those genetic differences influence the phenotype which is what is used in the somatic evolution of cancer.

    David

    rafefurst
    Hey David, thanks for reading and commenting.  I understand your concern, and as I'm sure you can appreciate there's a balancing act one must walk in "debunking" general misconceptions.  It's difficult to not go overboard sometimes and your criticism is fair.  
    What I would say in clarifying my position is the following:
    • The gene level is hardly important at all, but the genome/chromosome level is very important
    • To the extent that you are willing to call gene/genome all one thing (i.e. the "genetic system"), then yes, genetics are very important
    • That said, there is at least one level that is even more important, which is the cellular tissue leveel (i.e. the population of cells that are undergoing evolution).
    • Yes, "genetic heterogeneity" is a major driver for that evolution, but there is lots of evidence that non-genetic heterogeneity (i.e. in the microenvironment) is sufficient to cause evolutionary changes in cell behavior (of which cancer is born).
    • Not to overstate this, but the whole "mutator phenotype" argument is based primarily on non-genetic factors.
    • The larger point is that cancer is clearly multi-scale, complex, system-wide and with lots of feedback loops.
    • The scales that are important go beyond even the individual organism and into the social, sociotechincal and other higher order system dynamics.


    Rafe Furst http://emergentfool.com