Review of Bert Vogelstein “Bad Luck” Cancer Science pub

A new paper in Science by Bert Vogelstein suggests that a good part of cancer is attributable to bad luck.

There are so many big questions about cancer. They resonate with me very strongly as a cancer researcher and a cancer survivor myself (more on my cancer story here).

  • What really causes cancer?
  • Why does it feel sometimes like we are struggling so much in the “War on Cancer”?
  • What is the role of stem cells in cancer and are there “cancer stem cells“?
  • What can we do to better prevent cancer or treat cancer once it happens?

The new Science paper by Cristian Tomasetti and Bert Vogelstein from Hopkins seeks to provide some possible answers to these kind of fundamental cancer questions.

The paper, entitled “Variation in cancer risk among tissues can be explained by the number of stem cell divisions”, argues that the more that the normal stem cells of a given tissue proliferate over one’s lifetime, the more common it is to find cancers sprouting up in that same tissue.

This relationship was reported as significant with essentially an 80% correlation. You can see the relative correlation for specific types of cancer as well below in Figure 1 from the paper.

They postulate that the relationship between stem cell proliferation and cancer is linked together mechanistically by mutations that randomly arise in stem cells each time that they divide.

Bert Vogelstein cancer "bad luck" paper.
Data from Bert Vogelstein cancer “bad luck” paper.

The paper is summed up in the journal in one sentence: “Errors arising by chance during normal stem cell division explain more cancers than do hereditary or environmental factors.” It’s a very attractive notion, but how solid is it? I’m still thinking it through.

The authors argue that a substantial proportion of human cancer are simply due to bad luck. What this means, if you accept that notion, is that for those of us who get cancer much of the time there would have been nothing that we could have done differently to prevent it and further that the genes we got from our parents may not have played major roles. It’s an intriguing, provocative paper that makes some bold assertions, but there are some issues that leave some of the key issues remaining as theories.

The most difficult issue is how to consistently and accurately calculate the number of lifetime stem cell divisions in a series of diverse tissues. This is extremely difficult and it’s not difficult to imagine such calculations being off by one or more orders of magnitude. Going through their supplemental data frankly I still am not sure how convincingly this was achieved. It’s not a simple matter by any stretch of the imagination.

Another factor is that not all cancers are going to originate with stem cells. Some tumors arise from progenitor cells or from differentiated cells that de-differentiate.

Further, many organs have more than one type of stem or precursor-like population. How does one handle that in modeling?

It is also possible that epigenetics play a substantial role in the argued for proliferation-associated cancers. For example, with every stem cell division there may be an increased risk not only of mutations, but also of epigenetic changes (in some forms called epi-mutations) that over time transform the normal stem cells into cancer cells.

I found this paper very thought provoking, but it’s just a start in a way. Let’s see what others find when they attempt similar calculations.


Other folks’ take on the papers are more skeptical:

Bob O’Hara & GrrlScientist

Aaron Meyer


34 thoughts on “Review of Bert Vogelstein “Bad Luck” Cancer Science pub”

  1. Hi, Paul.

    Thanks for the interesting blog and discussion.

    With a background in epidemiology, the questions I have and would want to understand better (without having read the paper yet) are:

    How was lifetime risk determined? Generally when we think of risk, we think of incidence. To measure cancer incidence using today’s technology typically involves a level of screening, meaning we know someone did not have cancer at screen Time 1, and they did at T2. However:
    a) by nature of screening, we already have a biased sample, using a denominator of people who go in and get screened, which is not the same as the universal denominator of U.S. population health, so drawing conclusions about everyone and all types of cancer is tenuous
    b) this mixes up different types of cancer and assumes they are all the same and we have the technology to see the denominator of all cancers in the body. Rather, with screening we are catching many cancers that would not be otherwise detected clinically or symptomatically. There is some argument that some types of early cancer are ‘fixed’ within the body before they become a problem. Even without that argument, there are different molecular subtypes of cancer (e.g. breast)–some more deadly than others and some more amenable to screening (in other words, some of the more deadly subtypes are not as easily caught on screens and so crop up quickly in between screens).
    c) “the more that the normal stem cells of a given tissue proliferate over one’s lifetime, the more common it is to find cancers sprouting up in that same tissue” –those who get screened tend to be the ‘worried well’ and take better care of themselves. They also tend to eat better, etc which affects the molecular level of cell turnover, stem cell division, oxidation, and a bunch of other stuff I won’t attempt to understand.
    d) along the same argument, those who bank tissue are an even smaller (and more biased) subset of those who get screened. Let’s say they never got screened, who goes in for surgery (or is it all biopsy) is all different too.

    Point being, there are many possible sources of error and bias that could completely change the graphic and correlation, related to the measurement of lifetime risk, and our understanding of ‘what is a cancer’, as well as the correlation between ‘all of these cancers’ and stem cell divisions, to the point where I wouldn’t put much weight into this meaty Science article.

    On a related note, top scientists estimate that 50% of premature mortality is preventable. …..But they said that 100 years ago too. So what progress have we made with the billions and trillions we’ve spent? Because ultimately isn’t the goal quality and quantity of life?


  2. This study is a joke. It is pure scientific laziness to say that two-thirds of cancer are caused by “bad luck.” Why don’t we tack on “the wrath of God” while were at it? Basically, the scientists have hit a wall where they can no longer explain something. Yet unlike every legitimate scientist in history — where they simply admit they don’t know and then continue researching — these people instead say that they do have the answer — and it’s due to “bad luck.”
    So what exactly is the scientific definition of “bad luck”?
    And how on Earth is “bad luck” now considered to be a legitimate, measurable scientific influence? Did they ever consider that perhaps emotional well-being may provide key links?
    This is so beyond absurd you honestly couldn’t make it up. Wake up people. You’re being duped.

  3. It’s not “bad luck” it’s what you’ve been exposed to, IMO, particularly your exposure to “man-made radiation.”

    Increases in cancer have been monumental since humans have been exposed to “man-made radiation” from:

    (1) atomic testing conducted around the world
    (2) nuclear meltdowns such as Fukushima and Chernobyl
    (3) and since nuclear energy plants have been built around the world (nuclear energy plants release radiation into the air and water during their normal operations)

    This man-made radiation is now everywhere in our environment…food, water, air, rain, snow…causing constant exposure to humans.

    This man-made radiation can cause cell mutations and therefore Cancer…… and indeed has been proven to cause many cancers and other diseases such as heart disease, thyroid problems, cataracts, low fertility, etc.

    Dr. John Gofman proved that it only takes ONE exposure of radiation to mutate a cell.

    Learn more at:

    (a) study Dr. John Gofman’s research
    (b) — highly recommended
    (c) read “Cancer Lies”

  4. I found the Science paper provocative and interesting, but flawed in some of it’s basic assumptions and the finger-pointing at stem cells is, well, a little bit of sensationalism to sell copy.

    That increased cell division fixes mutations and more cell division fixes more mutations has been known for decades (and Bruce Ames wasn’t even referenced!). But the role of stem cells in probably not as simple as assigning all the cell division load of a tissue to them.

    As you already mentioned in your article, I also sifted through the supplemental data and it is used for convenience and is not convincing. Some of the stem cell numbers are based on one publication and the whole cell division load is then ascribed to these – and this is wholly wrong for the liver, for example, where the lifetime cell division load is mainly contributed by somatic cells (hepatocytes and bile duct cells).

    My only real gripe is that this poor scientific rigor is to be found in Science and from a great scientist like Vogelstein, I expect something better. However, as a teacher of science it does provide me with another case study for my students, on how to mislead yourself and others by not being rigorous and having your work critiqued by your peers.

  5. Unbelievable! 75% of most cancer is bad luck?

    No it’s not the GMO’s, it’s not the BPA , it’s not the chemtrails, not the EMF waves, not all the carcinogenic chemicals in your detergent and other household items, not radiation, viruses, stress, low vit D levels, hormones, vaccines, asbestos or even your genes. Yes all these things MIGHT play a small role but in 75% of cases it’s BAD LUCK.
    These so called doctors got payed for these findings …..Bad Luck….REALLY?

    So make a big bowl of GMO popcorn smothered in GMO synthetic margarine, and get a flu shot -just make sure you get to your doctors and get all the early screening tests money can buy. Please leave your brain at the door.

    Cells replicate their division. To say its bad luck is junk science. For example a vaccine with plant or animal DNA can shed and be taken up by our human DNA. The result can be a mutation. Add to that toxins, pesticides and in some cases genes and you have mutation in cell division and cancer.

    Like I always say follow the money……..

    Dr. Vogelstein of this study was payed 3 million dollars only last year to state cancer was a genetic disease and now he says bad luck.
    In summarizing his discoveries of the last 30 years, Vogelstein says, “Cancer is, in essence, a genetic disease.” . Even this study gives companies like Monsanto and vaccine manufacturers a get out of jail free card.

    So my obvious question is…. If the end game/bottom line take away from this “study” is early detection ….what new test is on the horizon and who is offering it and benefitting from it?

    Guess what the answer is… Dr. Vogelstein has been working in his lab on a new cancer DNA test called “Liquid biopsy” ( type of blood test ).The goal I read is to have every doctor make this test part of a standard check up and then treatment and surgery can begin, but first they have to figure out where the supposed cancer is.

    So whats the problem with early so called detection? We all have cancer cells and our cells divide 24/7. Truth is most cancer cells never mutate to the point of illness especially when a good immune system is present. The body can find and eliminate them.

    Health is not just physical it’s mental too. Early “detection” will lead to unnecessary surgery, mental anguish, increases in chemo and radiation. New protocols, standards and drugs.

    Now instead of looking at outward factors this study will have more people becoming complacent and feel helpless and looking to their godlike doctors for answers.

    This is a way of getting the healthy treated same as vaccines are a treatment on healthy individuals where no treatment is indicated…….FOLLOW THE MONEY.

  6. I share many of the doubts and questions regarding these findings, but my main question would be…obviously the root cause of cancer are these transcription errors/spontaneous mutations, but it seems to me there must be factors which increase or decrease the frequency of this kind of event in the genetic machinery, and thus ways to mitigate those factors to reduce the frequency. The body usually has a way of correcting things when they go wrong…is their no mechanism in the body that naturally responds to correct errors of this kind which can be supported or supplemented? And finally, what about the role of the immune system after the fact, i.e. the error/mutation occurs, cancer causing cells begin to proliferate and the immune system either responds well or doesn’t, so wouldn’t a strong, healthy immune response be the main factor whether the event is triggered by environmental, genetic or these random mutations? It seems like this paper doesn’t really tell us anything….

    1. de fet, you raise some good points. In a way this paper was as much theoretical as concrete with data. They made an intriguing argument, but their view was of cancer as a closed system, which is not reality. That can be useful for modeling, but there are other factors involved such as the environment (e.g. which could alter “normal” stem cell proliferation rates), the immune system, epigenetics, and more.

  7. This new finding is pure self-serving propaganda put out by the conventional medical establishment (and its many allied toxic corporate industries such as the oil, pesticide, GMO and other polluting-destructive cartels).

    For many years it had been known to science what causes cancer, such as environmental toxicants, estrogen, x rays but the acknowledgment of the real causes inculpates the medical industry (and other industries), so these criminal cartels deceptively direct public focus onto “genes” or “bad luck” or they put the blame on the person. On anything but the real truth. As an example, countless solid research evidence has found that low dose x-rays cause cancer, in particular breast cancer (source: Rolf Hefti’s ‘The Mammogram Myth’ ), but the medical business keeps telling the public that an x-ray is a tiny risk. It’s total hype.

    Medical journals are marketing organs of corporate medicine so that most scientific studies are highly biased, flawed junk.

    Believing you get the truth from the medical industry is like believing you get the truth from the political leadership of a corporate nation. It’s entirely foolish and delusional because both are representative of massive business interests.

  8. As a reporter who wrote about the study, I find the discussion about the paper just as interesting as the paper itself. But there are some misconceptions that need clearing up.

    First, “credentials” aren’t required to get the study. However, you do need $20. Get your plastic ready and go to:
    Terms of use say: “You may view, download, and/or print the article for your personal scholarly, research, and educational use. You may not (i) distribute a copy (electronic or otherwise) of the article without the written permission of AAAS, (ii) post the article on an electronic bulletin board or web site, or (iii) charge for a copy (electronic or otherwise) of the article.”

    Catherine Danielson, I’ll echo Shinsakan’s point about your error in claiming the study “essentially clears all environmental factors from blame,” which proved you didn’t understand the study, even as reported in the media. It’s good to have a healthy suspicion of ulterior motives, but important not to let suspicion substitute for fact.

    Brian Sanderson, the paper included much more information than just the data in figure one. I for one know well that correlation is not causation, in fact I used that phrase in my article. The cross-checking with the rates of mouse small intestinal and colon cancers provided corroborating evidence that the risk of cancer rises with the number of stem or progenitor cell divisions.

    As for my own article, (available at my Web link below), I sent it to Johns Hopkins for fact-checking before publication. And Science’s own news article on the study reiterated the point about cancer being predominantly caused by differences in the number of cell divisions.

    The paragraph below is taken from the Science news article:

    “Here’s how it works: Take the number of cells in an organ, identify what percentage of them are long-lived stem cells, and determine how many times the stem cells divide. With every division, there’s a risk of a cancer-causing mutation in a daughter cell. Thus, Tomasetti and Vogelstein reasoned, the tissues that host the greatest number of stem cell divisions are those most vulnerable to cancer. When Tomasetti crunched the numbers and compared them with actual cancer statistics, he concluded that this theory explained two-thirds of all cancers.”

    So if the media erred in interpreting the study, we had helpers in the scientific community.



    1. Bradley:
      Thanks for your insights. It’s interesting to me that most comments are from people who haven’t read the paper. Note that I have not commented (nor read the whole paper)!

      Speaking only for myself, I rarely have time to get all the way through a paper – the exception is when a reporter asks me to comment! In those cases, I read every word.

      You’re doing the public and the scientific community a great service by being so careful and thorough in your reporting on science. Thank you!


      1. Thank you for the kind words, Jeanne.

        Some of the most vehement critics of the media coverage seem to have other than scientific motivations.

        One critic opened his post with these words:

        “Yesterday’s Times has a front page story ‘Two thirds of cancer cases are the result of bad luck rather than poor lifestyle choices…’. (paywall)

        “That doesn’t match my preconceptions, so I looked for the story online. ..”

        As a commenter said on PZ Myers’ blog, “some people are ideologically opposed to the role of chance in our lives.”

        The critic says two-thirds of risk variation across cancer types doesn’t necessarily mean two-thirds of all cancers. I get that point. But he didn’t mention this paragraph from the study:

        “A linear correlation equal to 0.804 suggests that 65% (39% to 81%; 95%CI) of the differences in cancer risk among different tissues can be explained by the total number of stem cell divisions in those tissues. Thus, the stochastic effects of DNA replication appear to be the major contributor to cancer in humans.”

        It’s worded in a slightly different way in this paragraph from the study:

        “We show here that the stochastic effects of DNA replication can be numerically estimated and distinguished from external environmental factors. Moreover, we show that these stochastic influences are in fact the major contributors to cancer overall, often more important than either hereditary or external environmental factors.”

        Meanwhile, the New York Times also drew the same conclusion:

        “Random mutations may account for two-thirds of the risk of getting many types of cancer, leaving the usual suspects — heredity and environmental factors — to account for only one-third, say the authors, Cristian Tomasetti and Dr. Bert Vogelstein, of Johns Hopkins University School of Medicine.”

        So if the press is getting the study wrong, we’re getting it wrong in the same way. I suspect that isn’t random.

        1. Bradley,
          You do a great job as a reporter and science writer and your task of writing about science for a broad audience is very challenging. It is such an important role and there are fewer reporters specifically focused on science and medicine these days so I greatly appreciate your work and it has major positive impact.

          Sometimes a paper like this one comes along that is very thought-provoking, but also very complex (even though this paper seemed simple on the surface) in terms of what it really means (and doesn’t mean). It can take some time to hash it out and give it deeper thought. It’s part of the process.

        2. I’m the critic you quote. And I have no problem at all with the role of chance in our lives: in point of fact all cancers are caused by bad luck.

          However, there are major problems with the methodology of this paper. One of them is that it’s bad statistics to extrapolate from “two thirds of the variation in risk between cancer types” to “two thirds of the risk of getting many types of cancer”.

          1. Paul B, good to hear from you.
            Now perhaps you can fix the inaccurate title of your post, “Science by press release.” I’ll address that in a bit. But first from your post:

            Imagine a hypothetical world in which cancer occurs during stem cell division with some significant probability only if a given environmental factor is present, and that environmental factor is present equally in all tissue types. In this world cancer incidence across tissue types is perfectly correlated with the number of stem cell divisions, but nevertheless all cancer is caused by the environmental factor.

            This is the same argument Adam Jacobs tried on David Gorski. Gorski rejected it because it was impossible in the real world. Cancer doesn’t work like that. As an oncologist/researcher, he’s interested in treating real patients, not about some flaw in treating hypothetical patients in an impossible world.

            You can read more here on the discussion

            Now as for your “Science by press release” headline:

            The two-thirds of cancers caused by DNA errors claim was not only mentioned in the press release, but in an accompanying Science news article, and mentioned in the paper itself:

            “A linear correlation equal to 0.804 suggests that 65% (39% to 81%; 95%CI) of the differences in cancer risk among different tissues can be explained by the total number of stem cell divisions in those tissues. Thus, the stochastic effects of DNA replication appear to be the major contributor to cancer in humans.

            These two sentences are directly linked “Thus …” So they are intended to be read together.

            Finally, to make sure I wasn’t misreading the paper, I sent my article to two scientists and Johns Hopkins itself for fact-checking before publication.

            I’m sure you want to provide media criticism that reporters will value, but your attempt was wide of the mark.

            1. Your story starts with a misleading headline “Most cancer is bad luck”. It continues with an image categorizing melanoma as not caused by environmental effects, whereas in fact there’s a strong and well established link to UV exposure. Then it highlights skin cancer as an example of endogenous carcinogenesis, even though Vogelstein in the press release puts “skin cancer, linked to sun exposure” in the high-environmental-risk group. Are you happy with all that?

              However, my post is aimed primarily not at reporters but at lay readers looking for a discussion independent of the PR from John Hopkins. It bothers me that conclusions are being presented which are not justified by the statistics in the paper – Adam Jacobs in the conversation you linked to does a good job of explaining some of the reasons. If the paper were really showing what it claims to show, it would demonstrate that its statistics are compatible with its preferred model of carcinogenesis, and incompatible with competing models. But it does nothing of the sort.

              You’re right that the title of my blog post was not very well chosen – I’ll add a note to the post saying so.

  9. CBC News mentioned this paper and frankly their report was so superficial as to be useless to me. Unfortunately this paper is not public access. So thanks a heap for your review and Figure 1.

    The first thing I note is that lifetime risk of cancer is actually proportional to total number of cell divisions raised to a power that would be slightly less than 1. As best I can eye-ball it, a power of about 5/7.

    One interpretation of the power being less than 1 would be that organs with more cell divisions also have more protective mechanisms against cancer. Sort of what might be expected from evolution.

    But, in truth, there are a thousand ways to interpret such power laws (something I used to do a lot of in other fields of science).

    The 80% correlation is with respect to the log-transformed variables (I presume). What would be more relevant is the amount of variance in the untransformed life-time risk of cancer that is “explained” by the power function fit:

    C = a*D^b

    C lifetime risk of Cancer
    D total number of cell divisions
    a proportionality constant (from intercept of log-log relationship)
    b power (slope of log-log relationship).

    The question then becomes, how does “lifestyle” influence a,b,D?

    Given the usually compromised solutions spewed up by evolution, probably not in any consistent way — something positive in one regard might well be negative in another. And there is the rub, lifestyle is probably no more optimizable that life is optimal.

    And similarly, evidence-based medicine is certainly uncertain… growl.

    1. Just to make myself clear:

      The power function relationship is interesting and so is the variation about the power function. But both of these things, in and of themselves, tell us nothing about the degree to which cancer is random or dependent upon deterministic factors (including factors that might be manipulated in straightforward ways).

      The media message that 2/3 of cancer is random (implying you can’t do anything about it) is irresponsible. The data in Figure 1 (alone) cannot support such a conclusion.

      There is another problem, what exactly would “random” mean in this context… There is no simple delineation between random outcomes and deterministic nonlinear dynamics. And if cancer turns out to be a linear dynamical system, I’ll eat my hat.

  10. Actually, this isn’t about the Nadals question, but this piece itself (I’m not sure if this is going to show up as a reply to the above comment or not.) I have got to say that one question came to my mind instantly: who funded this cancer study? Sorry to be cynical, but when a study comes out that essentially clears all environmental factors from blame, I start to wonder if any of the funding came from, say, Monsanto. Whose interests might this study serve? Might we learn anything more if we follow the money? Maybe these questions have nothing to do with anything, but I think that they should be at least asked. We’ll certainly never find out the answers otherwise.

    1. ETA: Unfortunately, the general public has no way of finding out, because there’s no way to access that paper through the website without credentials. Public libraries do not carry Science articles unless they are at least one year old. Looks like I’ll be sneaking into the OHSU library again! 😉 (“Stop her… she’s trying to LEARN FOR FREE!!”)

    2. Here’s what the Acknowledgements say about their funding.

      This work was supported by the The Virginia and D. K. Ludwig Fund for Cancer Research, The Lustgarten Foundation for Pancreatic Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, and NIH grants P30-CA006973, R37-CA43460, RO1-CA57345, and P50-CA62924.

    3. If interests are being considered, the study would seem to primarily serve the interests of the authors, i.e., by publishing it (especially in Science), they get publicity and can further their careers/secure further funding for their research. This would be true regardless of who is funding the study. Regarding the financial interests of the funding agency, though, I am curious as to why a finding that chance mutations in dividing cells contribute strongly to cancer would automatically cause one to think that the findings were bought by corporate money and thus suggest that said findings are invalid. Such an approach, i.e., blindly prejudging (and dismissing?) research based on personal perceptions/biases without first assessing the actual merits/demerits of the study, seems to be rather dogmatic. I am wondering whether you would similarly call for accounting of the money trail for a study that finds a specific environmental cause for cancer, e.g., a pesticide or GMO, or whether such studies are automatically given a pass for conflict of interest because they are perceived to go against the interests of evil corporations? Also note that the study does not “essentially clear all environmental factors from blame;” it still finds that environmental factors play an important role, more in some types of cancers than in others. Therefore, its actual value to evil corporations would likely be less than a study directly showing that specific products of said evil corporations are not harmful.

      1. I’m really going to try to answer this thoughtfully. I was not prejudging and/or dismissing, and certainly not automatically. That’s why I used the words “wonder” and “ask,” and that’s why everything that I said was phrased as a question. That’s also why I stated that “Maybe these questions have nothing to do with anything, but I think that they should be at least asked.” And I *absolutely* would want detailed information about the money trail for the study you mentioned as well. All biases need to be investigated on all possible sides. I also did not use the phrase “evil corporations”; you, however, did use it, not once, but twice. I’m sorry, but these things are objective facts. There is absolutely no way to deny what is clearly written on the page.

        I am absolutely determined to read this full study. I do not have the luxury of university access. That means that I have to jump through an unbelievable number of hoops and spend a lot of time to get this information– but I’ll do it. Does that sound like “blindly prejudging” or “automatically dismissing”? How many people in the general public would actually go through all of that work? The librarian at OHSU said that she had never, literally NEVER, seen anyone with a public library card come in there to do research. But I have done it before, and I’ll do it again. I am not sitting in an ivory tower. I am a PATIENT whose only hope for a real cure lies in stem cell research. Some of us have a real stake in this. It is not theoretical for me, not some kind of mental game-playing– this is deadly serious life and death. Just as it is for the hundreds of millions of other people who have diseases and disorders that do not have cures or even treatments. We all deserve answers, and we all deserve to be taken seriously.

        1. I respect your plight and position, but you literally said “when a study comes out that essentially clears all environmental factors from blame,” which was both a mischaracterization of the findings even as reported in the mass media and, as you acknowledged, an attempt to summarize the study without considering its methods or actual results. Similarly, the suggestion that the results may have been influenced by the funders was purely based on the perception of the results without actually considering the methodology or merits of the study; this seems like prejudgment or bias to me because it suggests that findings that may be unpalatable to some will automatically be rejected by them if the funding source turns out to also be unpalatable. I deeply respect your going the extra mile to follow the latest research, and of course as a patient you have perhaps the greatest stake in the research. However, it is cavalier and dismissive to assume that those who build their lives and careers trying to understand diseases and develop therapies that work have no stake in the process or are just doing theoretical work or mental game-playing or sitting in ivory towers, etc. Yes, we all deserve answers, but it is important to both apply the questions and interpret the answers without bias, even when they tell us things we don’t expect or don’t want to hear. That is the only way that therapies that really work can be developed.

  11. Dear Professor Knoepfler, dear other experts,

    I would like to come back to two other stories in your blog, because of the current development.
    Have you seen Rafael Nadals comeback 2 hours ago in Dubai?

    I think this is not only good for tennis, it could be a great victory for the stem-cell-technology and for the stem cell based regenerative medicine.

    I would be very glad, if you could say your opinion concerning his therapy and the amazing outcome.

    I just summarize all we know about Rafael Nadals treatment:

    Because of serious injuries of his cartilage and his bones Rafa had to stop tennis for several month

    After no therapy had helped him, he tried a stem-cell-therapy in November

    This therapy seems to be a PRP-therapy and an additional application of mesenchymal-stem-cells. The mesenchymal-stem-cells seem to have taken from his own fat tissue.

    His therapy seems to be done in Barcelona

    After about 6 more weeks, he started to train tennis again. He said, he is feeling well and the pain has gone

    and now he has played his first match again

    it seems to be an amazings cure

    Do you think this is a small evidence that the application of mesenchymal-stem-cells could heal bones and cartilage?

    At this moment there are no studies, which support his therapy, but that doesn`t absolutely mean, that his therapy isn’t working at all.

    Please think about PRP, many physicians know that PRP could do a good job in some cases for already years, but the medical insurances still don’t pay for PRP-Therapy, because there are no big studies till today.

    So, sometimes it takes much time, until a new therapy is accepted, although it is working well.

    I really don’t know, exactly, what I should think about Rafael Nadals treatment:
    Is it the first step of a breakthrough in the new year or not? Of course it is no more than a case report, but a successful case report could be a big step.

    I am always skeptical, if I hear about new expensive treatments, but on the other hand I think, “who heals, is right“.

    And I would like to emphasize, Rafas therapy is not used to advertise for a doctor or any institute, because I can ‘t even find, where he got this medical application and who did it and furthermore I can not imagine at all, that one of the successfullest tennis-players ever, would give his name to advertise for an dubious therapy.

    Altogether, after discuising all arguments and facts, I think there is a big chance, that the discussed therapy-option is a new therapy, which could help and cure many people.

    So I would like to ask you, to spend your attention for another time to this theme and to say us your opinion about Rafas treatment.

    Thank you in advance.

    1. Do you know more about the therapy?
      Where is this therapy available?
      Do you think this therapy is safe? He got his own cell, so the therapy should be safe?!?
      His comeback is amazing and gives hope to people with cartilage defects.
      Thank you to everyone, who can give me more information about this.

        1. Just an addendum:

          You asked, if this kind of therapy would be safe, because he got own cells?
          I am just thinking about this, In my opinion the PRP-therapy (you get your own blood) is relative safe? (as far as I know)

          But I don`t know, if it would be safe to get an injection of your own cells (mesenchymal cells) in your joint.

          I don´t know not enough about this, but maybe anyone of the experts here could give us a short answer?

    2. Because cancer is characterized and defined as over-proliferation of abnormal cells within the body, cellular proliferation has been the focus of carcinogenesis research and target of cancer therapies for nearly 100 years. Yet today the vast majority of cancers remain incurable and lethal, if they escape curability with surgery. Cell proliferation is not a characteristic unique to cancer cells, but of all cells.

      In the Science article by Tomasetti and Vogelstein (1), they concluded:

      “These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions….. [cancer] is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells.”

      Cryde J. Dawe, a comparative pathologist, posed this question nearly 50 years ago:

      “If the dividing cells represent the cell population with the greater risk to mutate and develop cancers, why do mice have a greater rate of cancer than blue whales or elephants, which have million more dividing cells than mice and a much larger lifespan in which to develop tumors? (2)”

      Based on cancer incidence in wild mice, with a 3 year life-span and weight of 30 g vs. a 100 ton blue whale with a 65-year life-span, and using associated weight per year risk for developing cancer, every blue whale would be expected to have 20,000 neoplasms by age one year (2).

      Furthermore, despite 99% of the DNA of chimpanzees and humans being identical, and the similarity in tissues and organs, cancer is rarely observed in chimpanzees. Epithelial neoplasms such as lung, colon, breast, prostate, or pancreatic carcinomas are responsible for more than 50% of annual human deaths due to cancer, yet their incidence in great apes is less than 8% in all published literature (3).

      The cell behavior that we regard as “malignant,” including: cell autonomy; invasion and digestion of surrounding normal tissues; migration and colonization of distant organs; ability to develop resistance to drugs, temperature, or radiation; and ability to kill the host are not only characteristics of cancer cells, but of pathogenic or opportunistic unicellular organisms (bacteria, fungi and protozoa). Rudolf Virchow (1821-1902), the father of modern pathology, first pointed out the resemblance between the biological behavior of cancer cells and that of single-celled organisms when causing infections. He thought, incorrectly, that cancer cells were cells infected with bacteria and had acquired their pathogenic behavior from them. Others later postulated that the behavior of cancer cells was likely due to the re-expression of past traits and behaviors (atavism) derived from their past evolutionary experience as independent, single-celled organisms from which all cells in multicellular organisms originated. In other words, the behavior of pathogenic unicellular organisms, including: unlimited replicative potential; capacity for invasion, migration, and metastases; abilities to evade the host’s immune system, to generate multi-drug resistance; and to kill a host are what we define as “cancer” when one of our cells re-express these past ancestral traits (4).


      (1) C. Tomasetti, B. Vogelstein, Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347, 78-81 (2015).

      (2) C.J. Dawe, Phylogeny and Oncogeny. Natl. Cancer I. Monogr. 31, 1-40 (1969).

      (3) D.S. Beniashvili, An overview of the world literature on spontaneous tumors in nonhuman primates. J. Med. Primatol.18, 423-437 (1989).

      (4) (4) F. Arguello, Atavistic metamorphosis: a new and logical explanation for the origin and biological nature of cancer. (CreateSpace Publishing, Charleston, ed. 1, 2011), pp.17-74. [first edition].

      1. Thanks, Frank. These are very good points. Is your argument then that cancer is a lot more complicated than just stem cell proliferations and randomly acquired mutations? I agree. It’s interesting as well that Dr. Vogelstein has done so much research on the genetics of cancer and then this study from him kind of downplays genetics in cancer.

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