The complexity of cancer: A science-based view

Last week I participated in a panel discussion at NECSS with John Snyder, Kimball Atwood, and Steve Novella, who reported on the conference last Monday. What I mentioned to some of the attendees is that I had managed to combine NECSS with a yearly ritual that I seldom miss, namely the yearly meeting of the American Association for Cancer Research (AACR) meeting. There are two huge cancer meetings every year, AACR and the annual meeting of the American Society for Clinical Oncology (ASCO). AACR is the meeting dedicated to basic and translational research; ASCO, as the word “clinical” in its name implies, is devoted mainly to clinical research. Personally, being a translational researcher myself and a surgeon, I tend to prefer the AACR meeting over ASCO, not because ASCO isn’t valuable, but mainly because ASCO tends to be devoted mostly to medical oncology and chemotherapy, which are not what I do as a surgeon. Each meeting draws between 10,000 to 15,000 or even more clinicians and researchers dedicated to the eradication of cancer.

Having taken the Acela train from the NECSS meeting in New York straight to Washington, DC for the AACR meeting, I couldn’t help but think a bit about the juxtaposition of our discussion of the infiltration of quackademic medicine into medical academia with the hard core science being discussed at AACR. One session in particular at AACR highlighted what is one of the most significant differences between science-based medicine and the various forms of “alternative” medicine that we discuss here on SBM on such a regular basis. That difference, quite simply put, is the difference between the simple and the complex. “Alternative” medicine supporters often scoff at practitioners of science-based oncology, asking why we don’t have a “cure for cancer” yet—as if cancer were a single disease!—or why we haven’t made much more progress since President Richard Nixon declared “war on cancer” back in 1971. One part of the answer is that cancer is incredibly complicated. Not only is it not a single disease, but each variety of cancer is in and of itself incredibly complicated as well. To steal from Douglas Adams, cancer is complicated. You just won’t believe how vastly, hugely, mind-bogglingly complicated it is. I mean, you may think algebra is complicated, but that’s just peanuts to cancer.

On Tuesday morning, I attended a session that hammered home that cancer is complex. The session was called, appropriately enough, The Complexity of Cancer. It was chaired by Dr. Joan S. Brugge, professor of Cell Biology at Harvard Medical School and featured as speakers cancer stem cell expert Dr. Sean J. Morrison of the University of Michigan, as well as two faculty from UCSF, Dr. Lisa M. Coussens and Dr. Allan Balmain. Dr. Brugge spoke about mechanisms that control tumor cell anchorage, as well as the interface between genetics and metabolism in cancer; Dr. Morrison discussed cancer stem cells and how some tumors appear to follow the stem cell model while others didn’t; Dr. Coussens discussed how chronic inflammation can lead to cancer; and Dr. Balmain discussed genetic network analysis as a means of determining the susceptibility to cancer of various cells.

Right from the beginning, Dr. Brugge invoked Nixon’s war on cancer with a particularly appropriate observation, namely that the war has been far more difficult than anyone could possibly have ever envisioned in 1971. Back in 1971, in the wake of the discovery of the first oncogene, src, most scientists studied almost exclusively cancer cells, not appreciating the role of the surrounding matrix of normal cells and connective tissue in both preventing and modulating tumors. It’s true that, even back in 1971, scientists understood that the immune system has an important role in controlling cancer, but we lacked the tools to study this system in great detail. Since 1971, the list of discoveries about cancer has been long. Some examples include the discovery of many more oncogenes; tumor suppressor genes; the role of tumor angiogenesis in cancer; cancer stem cells; the rediscovery of the Warburg effect and metabolic derangements in cancer cells; and an enormous number of discoveries in tumor immunology. Each discovery helped us understand better how normal cells become tumors and how tumors grow, invade, and metastasize. But each discovery also led to additional complexities and more questions.

One characteristic that virtually defines a malignant cell in solid organs (as opposed to blood-derived tumors) is its ability to survive when not attached to other cells in its normal surrounding matrix of collagen and other connective tissues. This characteristic of tumor cells has long been recognized, having been first described back in the 1960s. Normal cells, when not attached to the proteins to which they normally cling, rapidly undergo programmed cell death (apoptosis). Apoptosis due to becoming detached is known as anoikis. Dr. Brugge started out discussing her interest in anoikis and understanding how breast epithelial cells survive detachment. Her talk ended up encompassing intracellular signaling pathways, metabolic derangements, and genetics. One observation that is likely underappreciated is that cells that undergo detachment develop metabolic deficiencies that lead to decreased ATP deproduction, decreased cellular energy (real energy, not the fake “energy” — or qi — that alt-med proponents often invoke), and ultimately programmed cell death. One of the more provocative observations is that antioxidants can actually help save these cells by neutralizing reactive oxygen species (ROS) and thereby rescuing fatty acid oxidation. For purposes of this discussion, the details aren’t important (although they are very important for cancer biology). What is important is that antioxidants are not a universal good when it comes to cancer; in the case of the models of breast cancer discussed by Dr. Brugge, antioxidants actually promote the survival of transformed cells because part of the mechanism by which these cells undergo programmed death is through the production of ROS. Does this result mean that antioxidants don’t prevent cancer? Of course not. It does however, when taken in context with other studies, suggest a great deal of complexity, where in some cases antioxidants prevent cancer and others may promote cancer.

Contrast this to the frequent alt-med claim that antioxidants prevent cancer and are virtually always good.

Dr. Morrison’s talk touched upon one of the most contentious issues in cancer today, namely the cancer stem cell hypothesis. This hypothesis goes something like this. There exist within cancer a population of cells that behave like stem cells. They are self-regenerating and each is capable of dividing indefinitely and recapitulating a tumor, while the vast majority of tumor cells have only limited replicative potential. The population of cells that can actually produce new tumors may be very small, much less than 1% of the cells in any given tumor. This concept has been most validated in leukemias, although there is good evidence that breast and a variety of other cancers may follow a stem cell-like model.

Cancer stem cell

Cancer stem cell

Under the stem cell model of cancer, these stem cells are highly resistant to chemotherapy, which wipes out all the non-stem tumor cells but leaves a few tumor stem cells, which can rapidly grow and then recreate the tumor, even from a single cell. In essence, the stem cell model postulates a hierarchy among tumor cells, as contrasted to the previous model, which was a more stochastic model in which any tumor cell could produce a tumor. To boil the concept down, in the stochastic model, any given cell in a tumor could be viewed as having, for example, a 1% chance of being able to form a new tumor if transplanted, while in the stem cell model only 1% of the cells of a given tumor can form new tumors, but they do so with very high efficiency. Moreover, these cancer stem cells have various protein and genetic markers that distinguish them from other cells in the same cancer.

The concept of the cancer stem cell is rather controversial. Personally, although the evidence has persuaded me that there is such a thing as what is commonly called a “cancer stem cell,” from my perspective I view the term as a poor descriptor of this cell mainly for semantic reasons. The term “stem cell” implies unlimited ability to produce different tissue types, which is not what this model is about at all. It’s long been known that tumors are made up of different populations of cells with different characteristics, and it’s not such a stretch to accept that many tumors might have a subpopulation of cells that are most responsible for tumor growth, with most of the other cells remaining quiescent or only slowly dividing. What Dr. Morrison argued is that some cancers follow a more “stem cell” model, while others follow a more stochastic model. He used the example of melanoma to illustrate this point: over 30% of the cells in a given melanoma studied can produce new tumors. While this observation might be consistent with the existence of a melanoma stem cell that makes up 30% of a typical melanoma, Dr. Morrison was unable to find any markers to distinguish the cells that could form tumors from those that could not, and he checked over 50 markers. While this does not entirely rule out a stem cell model (it’s possible that he hasn’t yet found the right marker), it is more consistent with a stochastic model, in which each cell in the melanoma has a 30% chance of being able to form a tumor when transplanted.

Why is this important? It’s important because it has great relevance to treatment. If a tumor is driven by stem cells, then to eradicate the tumor it is necessary to eliminate the stem cells. If it is driven by a more stochastic mechanism, a non-stem cell mechanism, then a “kill ‘em all” approach is more likely to succeed. Of course, it wouldn’t surprise me if it turns out that most tumors actually fall somewhere on a continuum between being stem cell-driven and being stochastic. Cancer is just that complex. The term “either-or” rarely, if ever, applies to it.

Dr. Coussens’ talk is fascinating for what it revealed about the immune system and cancer. How many times have you heard “alternative medicine” believers and promoters brag that this nostrum or that potion “boosts the immune system”? As we’ve said before here, it’s a meaningless claim, because sometimes boosting the immune system is bad, as in autoimmune diseases. In cancer, it’s long been known that inflammation, particularly chronic inflammation, can lead to cancer. One of the most classic examples of this phenomenon is how gastroesophageal reflux disease (GERD) can lead to inflammation in the lower esophagus, which can lead to a change in the cells there known as Barrett’s esophagus, which can ultimately lead to esophageal cancer. Inflammation is a function of the immune system; consequently, when you take anti-inflammatories, you are suppressing part of the immune system on purpose in order to decrease inflammation. In any case, Dr. Coussens discussed how activation of certain parts of the immune system can suppress cancer development, while activation of other parts can promote tumor progression. This slide, taken on my iPhone, demonstrates the concept:


Dr. Balmain echoed this message but came at it from a different angle, namely from the complexity of changes in gene expression in cancer, and how a highly complex interaction between inflammation, stromal cells, the immune response, metabolism, and changes in gene expression in a tissue, specifically skin, can influence susceptibility to cancer. One of the big disappointments in cancer research is that relatively few cancers have easily identifiable genes driving them, even though many tumors have a strong heritable component. The reason may well be due to the inheritance of multiple susceptibility genes of low penetrance, meaning that they don’t individually have a strong effect on the characteristics of a cell. Cancer actually involves changes in the expression levels of hundreds, if not thousands, of different genes. In fact, the way we now look at cancer is through network analysis of the levels of thousands of genes in the cell. We’ve gone from looking at single genes to looking at thousands upon thousands of genes. As Dr. Balmain concluded, cancer susceptibility and progression depend upon the emergent properties of many genes, each of which individually has a small effect, and these genetic variants affect the tumor cell, the microenvironment surrounding the tumor cell, or both. Moreover, depending upon the tumor type and situation, inflammatory networks can play opposite roles, either promoting or inhibiting tumor susceptibility and progression.

Is that complicated enough for you yet?

Then let’s move on beyond this talk. On Friday, a bunch of us on our floor on the cancer institute got together to discuss interesting stuff we saw and learned at AACR this year. One topic that came up is the Cancer Genome Atlas, or TCGA (you gene geeks out there may find the initials amusing, but they explain why the word “the” was included). The idea behind the project is to sequence the genomes of many, many cancers. You might wonder why it’s necessary to sequence so many cancer genomes, and it’s not an unreasonable question. The reason is that so many cancers are driven by different mutations that it’s unlikely that any two tumors have the same set of mutations driving them. Consequently, TCGA seeks to sequence at least 500 cancers for each cancer type studied. It started with a pilot project and has since been expanded to 20 different tumors. By sequencing lots and lots of tumors, or so the idea goes, we can identify commonly occurring mutations and sets of mutated genes, perhaps even across cancers, that can be targeted for therapy. At the very least, it is thought that we will be able to develop a greater understanding of the complexity of cancer.

I must admit that when I first heard of TCGA, I was skeptical. To me, it struck me as perhaps the largest fishing expedition in the history of cancer research. Moreover, even this massive undertaking is only part of the picture. As I alluded to earlier, the metabolism of cancer cells is often hugely abnormal, and a “chicken or the egg” argument continues to some extent even now about whether it is the metabolic abnormalities that drive mutations or the mutations that produce metabolic abnormalities. More likely, it’s a little of both, the exact proportion of which depending upon the tumor cell. None of this even considers influences outside of the genome (epigenetic influences) or differences in how proteins are made. Part of our discussion also pointed out that so many mutations have been associated with cancer and that they are often so different in different tumors, even from the same tissue, that trying to figure out which mutations found in TCGA are even relevant to cancer and which ones are actually driving the development, progression, and spread of cancer will be a daunting task, every bit as challenging as the Manhattan Project or sending a man to the moon in less than a decade. In fact, when you consider how vastly, hugely, mind-bogglingly complicated cancer is, it’s amazing that we do as well as we do now and that we’ve made as much progress as we have, arguments over whether we are too conservative or whether pursuing riskier research strategies will bear fruit faster notwithstanding.

Compare this to the view of many practitioners of unscientific medicine. My favorite example of a vastly, hugely, mind-bogglingly simple pseudo-explanation for cancer is that of the late Hulda Clark, who claimed to be able to cure all cancers (not just all cancers, but all disease) but who died of multiple myeloma herself. Her idea was that all cancer is caused by a liver fluke, which she would claim to be able to kill (and thus cure the cancer) with device she called her “Zapper,” a cheap little electrical gadget that looked as though it were assembled from spare parts at Radio Shack.

Another quack, Nicholas Gonzalez, claims that all cancer is due to a deficiency in pancreatic enzymes, for which he prescribes pancreatic enzyme replacement, up to 150 supplement pills a day, a “nutritional” regimen consisting of various vegetable and fruit juices , and a “detoxification” regimen including coffee enemas. He made a name for himself with a cherry-picked case series of his own patients that appeared to have survived pancreatic cancer far longer than is generally anticipated based on historical controls. This lead to a highly unethical clinical trial that ultimately showed that Gonzalez’s patients did considerably worse than conventional therapy, as poor as conventional science-based therapy does against pancreatic cancer.

These are not the only ones, of course. Still another quack, Robert O. Young, ascribes all cancer to “acidity” in the blood, and his treatment is always diet and bicarbonate to try to “alkalinize” the blood:

Robert O. Young

Young even goes so far as to describe cancer as a “poisonous acidic liquid,” states that “there is no such thing as a cancer cell” and that cancer cells are cells that have been “spoiled by acid.” To him, the tumor is the “body’s protective mechanism to encapsulate spoiled or poisoned cells from excess acid that has not been properly eliminated through urination, perspiration, defecation or respiration.” Young’s ideas have sucked in unwitting cancer patients, including one named Kim Tinkham, who even appeared on Oprah’s show a couple of years ago. (In addition, Young also doesn’t believe that sepsis is caused by bacterial infection.) On a related note, another quack named Tullio Simoncini espouses a variant of Robert Young’s ideas in that he believes that all cancer is a fungus. The similarity is that he prescribes “alkalinization” for the fungus, some of which can involve injecting sodium bicarbonate directly into tumors.

If there’s one difference between science-based medicine and quackery when it comes to cancer, it’s that science-based medicine appreciates the sheer complexity of tumors, while quacks often go for risibly simplistic pseudo-explanations of cancer. The complexity of cancer as a set of related diseases is incredible. Indeed, one has to respect it and even stand in awe at its ability to grow, evolve, and ultimately develop resistance to almost any treatment we can come up with. That’s not to say that the situation is hopeless, but it is an explanation as to why, nearly 40 years after Nixon’s war on cancer commenced, our progress against this foe has been incremental. Despite this record, I remain nonetheless optimistic and expect this situation to change within my lifetime. The reason is that we are finally developing the tools, both scientific and technological, along with the computational power to analyze the data, that hold out hope of an understanding of different cancers deep enough to make real progress in reducing the incidence, morbidity, and mortality from cancer. This isn’t any comfort to patients suffering from cancer now or to those who have (as I have) lost loved ones to cancer, but it does give me hope that, should I be one of the unlucky ones who develop cancer, my chances of survival will be better than at any time in history.

No quack can even come close to giving me that sort of hope.

Posted in: Cancer

Leave a Comment (44) ↓

44 thoughts on “The complexity of cancer: A science-based view

  1. Draal says:

    “What is important is that antioxidants are not a universal good when it comes to cancer;”

    Which specific antioxidants are talking about?

    Antioxidants covers a broad ranges of chemicals including the ones our bodies need (eg. acetylcysteine and vitamin C), dietary antioxidants (eq. plant derived polyphenols and carotenoids), and synthetic compounds (eq. EDTA, BHT and BHA).

  2. David Gorski says:

    Exactly. Antioxidants encompass a large range of chemicals, making any generalizations about them perilous.

  3. Zoe237 says:

    Fascinating stuff! I’m curious about vitamin d, as it is recommended for infants and toddlers. Does this fall under the dreaded supplement category? Should children be taking a multivitamin? Also, does stem cell research show any promise for cancer?

  4. passionlessDrone says:

    Hi David Gorski –

    Great article! Thanks a lot; I’m seeing a lot of simiarities to my preferred domain.

    Your thoughts on antioxidants is particularly interesting. It seems possible that while antioxidants might in preventing cancer, they can do the opposite once you have a tumor. And as you make clear, with lots of different ways to get the ball rolling, an antioxidant approach to prevention doesn’t do it all.

    I saw a Nova a while ago regarding the potential use of biomarkers; i.e., increased VEGF, as tools for identifying the presence of some types of tumors without having to wait for a lump or pain to be present. I’d be curious on your thoughts regarding this.


    – pD

  5. superdave says:

    This was an exhaustive review and still however complex cancer seems to be indicated by this article its probably at least 100 times even more complex.

  6. daedalus2u says:

    Nice article. But just remember, however complicated cancer cells are (and they are extremely complicated), “normal” cells are much more complicated.

    Cancer cells are cells that have had “normal” regulation removed, usually by deletions of certain genes. Cancer cells are thus more simple than normal cells with those pathways still intact.

    Normal cells seem simple because they seem to act in normal, boring, consistent and predictable ways. The normalcy of behavior belies the complexity of regulation that keeps everything looking “the same”.

  7. David Gorski says:

    Actually, I disagree. Cancer cells are just as complicated as normal cells, only in different ways. Cancer as an “organ” is just as complicated as almost any organ I can think of (other than perhaps the liver or brain), only in different ways.

  8. Oooh, cancer as an organ. I like that. I mean I don’t, it’s horrible, but it’s a good image.

  9. Draal says:

    “Cancer cells are just as complicated as normal cells, only in different ways.”

    That’s exactly what systems biology would predict.

  10. Alison Cummins – Oooh, cancer as an organ. I like that. I mean I don’t, it’s horrible, but it’s a good image.

    Yes, a very compelling way to communicate the concept with extra points for SciFi, mad scientist flair.

  11. gaiainc says:

    Vitamin D for infants and children is interesting, particularly if you read the evidence that the AAP based their recs on. The recommendation is not a good example of science-based medicine, IMHO, but given that I live above the 45th parallel and a lot of my patients don’t get the sun they need, it’s not necessarily unreasonable to increase how much vitamin D they do get.

    Every time someone grumbles to me about how medicine can’t find a cure for cancer, I usually have to resist the urge to explain to them why there will never be a cure for cancer since cancer is not a single thing. My currently analogy is that cancer is like mammals. Sure, there are a lot of similarities between mammals but there sure as heck a lot of differences. What works for one mammal does not work for another.

  12. Scott says:

    Heh – “cancer is like mammals” immediately started me thinking about a “cure for mammals.” That would be quite interesting, too.

  13. Maz says:

    To say that cancer is less complex because it consists of normal cells with safeguards removed is a bit of a stretch.

    While cancer cells do tend to lack a slew of regulatory and/or signalling pathways, they still manage to function.

    It’s like if you opened up a TV or car, switched a bunch of wires around so the TV only showed upside-down satellite feeds from Guam or the car could only drive backwards while honking with the radio set to classic rock.

    The cancer not only survives with the normal functions/safeguards removed, but continues to operate and recruit normal physiological functions to aid its spread. The fact that cancer continues to work, but in a haphazard and destructive way, makes it MORE complex and dangerous.

    At least with normal cells we can feasibly ask “What is the advantage does this feature confer to the organism?”

  14. Draal says:

    While cancer cells do tend to lack a slew of regulatory and/or signalling pathways, they still manage to function. ”

    That’s not exactly how I would put it. Consider all the different cell types in the body. Same DNA, but different phenotypes due to regulatory elements and other stuff. Cancer cells are just another cell type with a different phenotype (and yes, an ever so slightly different genotype but all cells can accumulate mutations as they age).

  15. pmoran says:

    Thanks David. Very informative, for that majority of us who are unable to keep up with this massive field.

    I, too, baulked at the notion of a “cancer stem cell”, but for another reason. I reasoned that the marked variability of appearance of the cells in most cancers under the microscope, with many having nuclear defects that should be inimical to successful cell division more or less predicts the observed findings.

    Allusions to “the discovery of the cancer stem cell” glorify a rather trivial finding, in my view.

  16. JMB says:

    A stochastic model can be used to simulate/approximate the growth pattern of tumors with stem cell growth patterns. The differential equations used for the iterations are just modified from the more traditional models as shown in the diagrams.

  17. superdave says:

    dont disregard that complex behavior can result from simple systems. even cancer is simpler than normal cells they are probably negligably so

  18. Draal says:

    Stochastic models like Flux Balance Analysis (FBA) and Minimization of Metabolic Adjustment (MOMA) are solved using linear algebra (specifically, linear and quadratic programming, respectively) not differential equations.

  19. daedalus2u says:

    I think people are missing my point. What people mean by “complexity” is not well defined. I think that people are using the term “complex” to be synonymous with “different than any other type of cell”. Cells that are called “cancerous” are considered “complex” because they are very different from other cells and behave in ways that are completely idiosyncratic for that type of cancer which may well be unique.

    Many cancers have large parts of the genome deleted and are grossly abnormal. Yes, they still function in spite of the genetic deletions they have experienced. A loss of information (through deletion of genes) is a reduction in complexity.

    I am not saying this to dismiss the complexity of cancer cells, but rather to emphasize the complexity of normal cells, a complexity that is cryptic because the cells are “normal” and we don’t understand how they function. We observe that they function “normally”, which we are conditioned to think is “simple” because it is common, our brains are configured to notice differences, and attribute complexity to the differences that we can observe.

  20. Draal says:

    “A loss of information (through deletion of genes) is a reduction in complexity.”

    Not exactly. For example, gene deletion of suppressors will remove the brakes that can control the growth rate of a cell. So an intact suppressor prevents RNA synthesis while deleting it will increase RNA synthesis. More “information” is being transcribed without suppression.

  21. JMB says:


    Thank you for the correction. Obviously I need to refresh my memory and/or get more up to date. I’m an old C hack who hasn’t kept up to date (although I do have R and Mathematica). I guess I’ll have to find some tutorials.

    Thank you Dr Gorski for the article with a glimpse at current concepts. I forgot to say that in my first post.

  22. Draal says:

    np. I’d recommend using Matlab to solve linear programming problems but you’d need some specialty software package like CPLEX to solve the quadratic programming stuff.

  23. daedalus2u says:

    Draal, a system that has a capacity and is also self-regulating of that capacity is more complex than a system with the same capacity but without any regulation.

    The regulation is (usually) more complex than the thing it regulates. The sum of regulation and the thing regulated is always more complex than just the thing.

  24. Draal says:

    daedalus, I understand what you are saying but let me take one more stab at it. Cancer cells frequently have deletions or inactivation of repressors that would normally control growth. When modeling the entire metabolic network, each gene is attributed to a protein which in turn is associated with a chemical reaction(s). Solving then entire dynamic system is not impossible but computationally, it’s extremely impractical. So to cut the problem down to size, assumptions are made. For one, we can assume a psuedo-steady state (i.e. all changes in fluxes are zero) which is fairly valid on a short enough time scale (say several minutes). A dynamic model with time scales of several seconds can be incorporated but lets just stick to the SS assumption.
    Each gene is assumed to be either on or off (1 or 0) and the gene is mapped to their respective reaction(s) (1 if the reaction is active or 0 if it isn’t). More genes on means more reactions. In other words, the degrees of freedom are greater for systems with more reactions going on.
    A repressor would be modeled as the removal of a gene or a whole slew of genes, and therefore it simplifies the math. Removal of the repressor would introduce more reactions into the problem and increase the solution space for which the answer(s) to the system resides. You can have multiple solutions to a problem (the sqrt of 4 is both 2 and -2); some physically possible, some not.
    Now, stepping back, the incorporation of a repressor into a system seems as if you introduce more complexity because now you have system with an extra component but it’s the nature of the repressor which is key. A repressor will be modeled as an initial condition. A system without a repressor has a bigger solution space because there is less limitations. Adding a repressor will shrinks the solution space because it remove variables from the system. In fact, the repressor solution space fits within the solution space when no repressor is present.

    In a nut shell, I view this problem mathematically versus philosophically and conclude that for psuedo-steady state systems are less complicated when repressors are active.

  25. David Gorski says:


    Actually, what makes you think that cancer cells–or cancers, which are made up of tumor cells, stroma cells, and blood vessels, don’t have self-regulating capacity? They do. It’s just different and part of that difference is that the tumor no longer responds the way normal tissue does to regulatory signals to stop its growth. Moreover, evolutionary forces on tumors result in its developing into a population of many different clones, each either slightly or very different from the rest, leading to a great deal of complexity based on the sorts of cells existing in the tumor.

  26. Speaking of cancer being complicated, I was just checking in at the Pepsi “refresh everything” campaign to make sure that Jenny McCarthy is not going to get $250k, and she’s not. (She’s number 30.) So that’s good. But do you know who is the leader in the $250k category? In first place?

    The Kanzius Machine.

    “Develop an alternative cancer treatment that has no side effects”

    “Current treatment methods of chemotherapy and radiation therapy are both physically debilitating and expensive. John Kanzius’ theory of using radio waves to stop cancer offers a better way.

    “Early research has focused on pancreatic, liver, breast, prostate, colon, lung and leukemic cancers. The preliminary findings indicate that the Kanzius Radio Wave Cancer Treatment is non-invasive – that is, no surgery is needed and 100 percent of the cancer cells are destroyed without damage to neighboring “good” cells or tissues!”

    They want the money for fundraising.

  27. The Kanzius Machine – huh – certainly sounds to good to be true, but after googling about and a quick search on quackwatch, scienceblogs and here I couldn’t find anything that indicates it’s a scam. Anyone heard anything on it?

  28. Try googling Kanzius Quack.

  29. oderb says:

    Whether on not Dr Gonzalez is a quack I believe one cannot easily dismiss the research and theories of Dr John Beard, whose work is the basis for Dr Gonzalez model of how cancer develops and can be treated.

    Dr Gonzalez recently published a book “The trophoblast and the origins of cancer” New Spring Press 2009, which is an impressively researched and convincingly argued text that concludes that Dr Beard was the first to identify the adult stem cell – which he called a vagrant germ cell; that he solved the mystery of where adult stem cells come from – the embryonic yolk sac – which still eludes modern researchers; and that it is the trophoblast created from the germ cell which is in fact cancer.

    Whether or not pancreatic enzymes are or are not the antidote to the trophoblastic cancer cell is not the issue I am addressing. Clearly those who blog here have no belief in that theory.

    What I would like to request is someone point me to a detailed scientific rebuttal of the central arguments and conclusions of Dr Beard (and thus Dr Gonzalez) regarding the origins of many if not most cancers.

    For if Dr Beard was largely correct 100 years ago, his work deserves to be looked at more closely for its insights into the origins and treatment of cancer even if one entirely dismisses the clinical approach of Dr Gonzalez.

  30. JMB says:

    IMHO the Kanzius Machine is still a technology in development. The eventual success would depend on the ability to selectively concentrate particles with high microwave absorption rates in tumors. It is not quackery yet, because it is plausible, and it is not yet offered as treatment to the public. They are just seeking research funding.

  31. squirrelelite says:


    You wrote:
    “What I would like to request is someone point me to a detailed scientific rebuttal of the central arguments and conclusions of Dr Beard (and thus Dr Gonzalez) regarding the origins of many if not most cancers. ”

    Science is not about proving a negative, although carefully conducted tests can reduce the probability of stated hypothesis being true to a very low number. However, I am fairly confident that most working research scientists don’t have time or money or interest in chasing down and disproving every unsupported assertion that is made to them. I would guess they much prefer to concentrate on the areas that seem promising and interesting. If Dr Beard’s “conclusions” had seemed promising to some people, the onus was on them to plan, conduct and document tests that demonstrated it. That is what research is about.

    Since the main people trying to follow up on Dr Beard’s ideas have been Gerson, Kelly, and Gonzalez, those ideas don’t seem to have been a fruitful area of research into effective cancer treatment. In fact, Dr Gonzalez’s treatment has proven to be worse than the standard.

    For a good general discussion of the Gonzalez protocol and its connection with Dr Beard, I suggest this article from Quackwatch:

    Dr Kimball Atwood wrote an excellent series of articles on the Gonzalez Trial starting with this one:

    Dr Gorski more recently discussed the Gerson Protocol:

    Can you name one form of cancer for which Dr Beard’s ideas have been shown to provide an accurate description of its origin or development? Do you have a reference?

    Has an effective treatment for that cancer been developed and demonstrated to be superior to standard therapy (surgery/chemotherapy/radiation therapy as appropriate)? Where were the results published?

  32. pmoran says:

    I cannot marshal all the evidence in one post, but there is ample evidence that cancer usually develops from the previously well-differentiated native cells of the organ of origin and not from Beard’s embryonal rests or pluripotent stem cells. His theory had some very brief popularity because trophoblast can behave and look a bit like some types of cancer.

    However, for many tissues intermediate stages in the development of cancer have been observed e.g. polyp —> cancer, cervical dysplasia. Many cancers seem too closely related in character and function to the cells of the tissue of origin to have arisen otherwise.

  33. oderb says:


    I would argue that the biases of medicine (new is better than old – Beards’ work is 100 years old) patentable is better than natural (pancreatic enzymes vs drugs), insiders are to be trusted not outsiders (Beard being an embryologist and not a cancer researcher) and the necessity of overturning of the cancer orthodox paradigm of normal cells suddenly going astray if Beard was right all contribute to the lack of research and testing of Beards’ theory.

    Isn’t it interesting that the on rigorous study of pancreatic enzymes to be published – in the reputable journal Pancreas in 1994 – showed that the enzymes extended the life of the mice and slowed tumor growth. P<.0002.


    Does anyone truly believe that if a drug company had found a treatment that extended the lives of mice with pancreatic cancer that there would be no further testing? Sure.

  34. David Gorski says:

    Isn’t it interesting that the on rigorous study of pancreatic enzymes to be published – in the reputable journal Pancreas in 1994 – showed that the enzymes extended the life of the mice and slowed tumor growth. P< .0002.

    Isn’t it interesting that the Gonzalez regimen, which involves giving patients lots of pancreatic enzymes, turned out to result in survival three times shorter than standard gemcitabine-based chemotherapy, a result published in 2009?

  35. squirrelelite says:


    I guess a non-answer means accurate description is a no and superior therapy is a long, rocky row to plow.

    As for pancreatic enzymes (or whatever), you’ve got 80 or so years of research and one 16 year old study with mice to suggest something that might help. And, as Dr Gorski noted, the Gonzalez regimen test doesn’t make that look too promising either.

    Any other good ideas?

  36. oderb says:

    Neither Gorski nor squirrelelite as expected answered my question – if a pharm drug significantly extended life in mice with pancreatic cancer, millions of dollars of research would be flowing in followup studies. But not a penny apparently was spent to follow up with additional animal studies, which SBM routinely recommends before human trials of unproven substances. Why Why Why? Aren’t you even a tiny bit bothered that such a significant research result led to…nothing?

    Instead you once again flog Gonzalez scandalously flawed study, which I purposely did not want to bring into the discussion, because my focus is on Beard and enzymes and not coffee enemas and the 100 other supplements and special diets etc which is the Kellly/Gonzalez protocol but which has little to nothing to do with Beards’ theories. (I have commented several times in previous posts on Gonzalez, and unlike any of you, I have been a patient of his for 20 years and know him to be a man of total integrity, compassion and brilliance)

    And as for pancreatic enzymes 80 year history squirrlelite Gonzalez devotes a considerable portion of his book to the issue of the quality and efficacy of pancreatic enzyme preparation over the decades and concludes – quite convincingly in my opinion – that until recently one couldn’t expect consistent quality from enzymes that were formulated with less than optimal biological activity. So we don’t have 80 years of valid research.

    And what exactly is wrong with a 16 year old study? Maybe you ought to critique the substance of the study (which I assume you cannot do) and not that it was done in the dark ages of the 90s. Is there a statute of limitations on scientific research? If there is maybe you can write a post on it.

    I challenge even one person here to read the book and then make a cogent argument against what Gonzalez argues. I know it’ll never happen of course. Disappointed with the close mindedness here – yes – naive, no.

  37. Chris says:

    Actually, the linked abstract was from 2004. Though, the not so exciting bit in the conclusion was “The data indicate that the beneficial effect of PPE on survival is primarily related to the nutritional advantage of the treated mice.” Yawn.

    Sad to say, no one will be able to answer your questions of why you have been able to survive for twenty years. The reason is that your statements do not constitute actual data. Even if you release all of your medical records to third party unbiased scrutiny, you are still a data point of N=1.

    What the data do show is that Gonzalez and human trials of your pet theories are not promising (see the Dr. Gorski’s blog posting that he linked to).

    To answer your question “What I would like to request is someone point me to a detailed scientific rebuttal of the central arguments and conclusions of Dr Beard (and thus Dr Gonzalez) regarding the origins of many if not most cancers.”

    Well, the way to answer it is for you to produce the studies that replicate Beard’s studies several times over. One study does not prove the effectiveness of a treatment, but several over the years done on different populations and repeat the same results. One needs to show that the preponderance of data show effectiveness. Not a guess. Not a single book. But lots of agreement of results. Do you have those handy?

  38. squirrelelite says:


    Thanks for your response. I’ll try to offer my thoughts on your questions and perhaps Dr Gorski can correct me if I wander too far astray. (I’m coming at this from physics and chemistry and don’t have access to most medical pubs to check things out in detail.)

    I am curious too. If the results had been as promising as you seem to think, I would have thought that some of the 10 co-authors of the Nebraska study you mentioned (including #8, NJ Gonzalez) would have been submitting lots of grant applications over the next several years (as Dr Gorski has been doing) to do follow-up research. Maybe, grant funding was a little bit tight under the Clinton administration. Still, it looks like NJ Gonzalez found enough funding to do a “2-year, unblinded, 1-treatment arm, 10-patient, pilot prospective case study” to assess the effect:

    If my rusty memory serves me right, I think Dr Gorski has already discussed this. I did a Medline search for pancreatic enzyme extract and found 50 articles, but most of them had little or nothing to do with its use in treating cancer. (There was stuff on folate and zinc supplements, for instance.)

    However, I did stumble across this interesting study that was just published a couple weeks ago. I don’t know if it has anything to do with the recently announced results of the Gonzalez test or not (Gonzalez was not one of the authors), but the results were similar:

    As the abstract notes that the patients were self-selected for which group they were placed in and

    “the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values”

    It then goes on to note:

    “At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P < .01). CONCLUSION Among patients who have pancreatic cancer, those who chose gemcitabine-based chemotherapy survived more than three times as long (14.0 v 4.3 months) and had better quality of life than those who chose proteolytic enzyme treatment."

    The Gonzalez study has certainly been flogged a few times on this blog, as I cited in my earlier links, but I don't know if morale has improved yet or not. ( :) ) If I continue to do so, it is merely because he (along with Gerson and Kelly) seems to have been the chief researcher to pursue Dr Beard's ideas. He was a co-author on your reference and my first one. I'm glad you like him as a doctor, though.

    I don't have convenient access to his book. But, I am curious. How did he measure "the quality and efficacy of pancreatic enzyme preparation" and do you know if he took advantage of those assessment techniques to assure the efficacy of the enzymes used in his much-flogged study?

    There is nothing per se wrong with a 16 year old study. James Lind's study on scurvy was over 250 years ago and is still cited as a pivotal step in the beginnings of modern medical research. But, it showed real, beneficial medical effects in human subjects. The study you chose to cite was a preliminary study on the survival effects on mice that had malignant human cells transplanted into the pancreas to cause tumors. I don't have access to the detailed results and can't critique them directly. The abstract says that the increase in survival was enough to be "significant", at least statistically, but the abstract doesn't say how much the increase was, so it is hard to guess their real importance. Based on the skimpy follow-up research and the recent Gonzalez results and the second link I cited, I would guess that the results were not "jumping up and down and cheering" significant.

    I doubt if I'll spend any of my limited funds to buy Gonzalez' book, but perhaps our city library system has a copy. However, unlike 250 years ago when James Lind published his results in a book, the current standard for adding research results to the scientific literature is in peer-reviewed research journals. He is probably right if he says that 40 or 50 or 80 years ago enzymes were not prepared with consistent quality. And based on Gonzalez' peer-reviewed research results, I am dubious that I will find it as convincing as you do. But, perhaps I will be surprised. It is one of life's little pleasures.

  39. JMB says:

    “Aren’t you even a tiny bit bothered that such a significant research result led to…nothing?”


    As Chris pointed out, from the abstract of the research, “CONCLUSIONS: The treatment with PPE significantly prolongs the survival of mice with human PC xenografts and slows the tumor growth. The data indicate that the beneficial effect of PPE on survival is primarily related to the nutritional advantage of the treated mice.”

    Pancreatic insufficiency is a well recognized and studied clinical problem in which progress has been made for treatment. Pancreatic insufficiency can result from tumor growth in the pancreas, or from resection of the pancreas to debulk the tumor, or from pancreatitis due to various causes. As also noted in the abstract, there are several consequences of nutritional deficiencies that may result from pancreatic insufficiency, “All mice in the control group showed steatorrhea, hyperglucosuria, hyperbilirubinuria, and ketonuria at early stages of tumor growth, whereas only a few in the treated group showed some of these abnormalities at the final stage.”

    Treatment for abatement of pancreatic insufficiency is already considered standard care for patients following surgical resection, or those with symptoms or laboratory findings of pancreatic insufficiency.

    Death from cancer may occur from several different types of complications, including infection, infarction, embolism, hemorrhage, or cardiac arrhythmia (which can be caused by ketosis, a companion to ketonuria). The listed complications are the final common pathways for death from many different types of cancer. Those complications are in turn the result of other metabolic problems induced by the pattern of spread of the cancer, or the metabolic activity of cancer. Mortality in cancer can be delayed by supportive care, and that can explain the reported reduction of mortality in the experiment (as suggested by the authors). Since that type of supportive care is currently accepted in standard treatment protocols, why spend millions of dollars for research (or subject more animals to research)?

    Now, it is quite possible for a different type of cancer to metastasize to the pancreas (such as malignant melanoma), and require pancreatic enzyme replacement. In which case it is provided as supportive care (just like antibiotics may be prescribed for an infection occurring with the cancer). So other types of cancer are sometimes treated with pancreatic enzymes, when pancreatic insufficiency becomes evident.

    However, supportive care is different than curative treatment. We don’t expect antibiotics, diuretics, anticoagulants, or pancreatic enzyme supplements to cure the cancer. The supportive care just helps the patient avoid a complication until later in the disease progression (or avoid it if there is time for the tumor to regress).

    Pancreatic enzyme supplements are already approved for treatment of pancreatic insufficiency, so subsequent trials were performed on human subjects, rather than pursuing more animal trials. As noted by Dr Gorski, the single human trial had such dismal results, it was not repeated. It would be considered unethical to subject patients to randomized clinical trials, when the initial results were so dismal.

    If pancreatic enzymes fail to reduce the mortality compared to chemotherapy in patients with pancreatic cancer, then why expect it to have an effect on other types of cancer?

    If the mouse experiment was repeated, and the control group was given chemotherapy rather than nothing, what would you expect the result to be? Is it even worth doing since the experiment has been done in humans?

    I think the problem here is confusing supportive care with curative treatment.

  40. JMB says:

    By the way, the confusion of supportive care with curative treatment was also the foundation of many of the arguments following the article on ““Vaccines didn’t save us” (a.k.a. “vaccines don’t work”): Intellectual dishonesty at its most naked”.

    Doctors don’t think of supportive care as curing disease. It can save a life, but supportive care doesn’t cure a disease. The people whose lives are saved may still have long term health problems. Vaccines prevent the disease (and most all the serious sequelae), and so are considered by doctors to be the cure.

  41. squirrelelite says:


    Thanks for pointing out the nutritional and supportive versus curing aspects of this treatment.

    Since my background in biology and medicine is more limited, I sometimes miss or just overlook connections like that.

  42. oderb says:

    Thanks JMB, Chris and Squirelliete for your thoughtful replies. I happen to have my semi annual apt with Dr Gonzalez next week and I will ask him to respond to your comments, and I report such here.

    @squirellite the abstract you linked to in P1 to is the same study released last year that was discussed in depth on SBM.

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