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Meet the 1 doctor in America who has no opinion on whether cigarette smoking contributes to lung cancer in human beings.

Paul Alper writes:

In your blog today you once again criticize Tol’s putative results regarding global warming: “At no point did Tol apologize or thank the people who pointed out his errors; instead he lashed out, over and over again. Irresponsible indeed.”

Well, here is something far more irresponsible and depressing. Read Susan Perry:

Why would physicians testify that smoking isn’t addictive? Money. Lots of money.

Here’s a finding, however, that may make that willingness seem less shocking: Tobacco companies pay the doctors handsomely for their testimony — up to $100,000 per physician per case.

Perry is referring to this paper by Robert Jackler, “Testimony by otolaryngologists in defense of tobacco companies 2009–2014.”

In response, I pointed Alper to my article from a few years back on statisticians and other hired guns for the cigarette industry. Among other things, it caused me to ratchet down my respect several notches for cigarette shill Darrell Huff. But most amazing was this exchange from Kenneth Ludmerer, a professor of history and medicine at Washington University in St. Louis:

Q: Doctor, is it your opinion that cigarette smoking contributes to the development of lung cancer in human beings?

A: I have no opinion on that.

The guy has an M.D. and he teaches at one of the nation’s top medical schools. All I can say is, I wouldn’t want this guy as my family doctor!

After reading my article, Alper wrote:

Did Rubin really receive over $2 million? When I was in graduate school at Madison in the late 1950s, early 1960s I attended Fisher’s lecture where he asserted smoking does not cause cancer. His then son-in-law, George Box, headed the stat department and was duly embarrassed.

P.S. Dr. Ludmerer is the “Mabel Dorn Reeder Distinguished Professor in the History of Medicine.” I googled Mabel Dorn Reeder and came across this obituary. I was curious if she’d died of a cigarette-related illness but it doesn’t say. I see here that she attended graduate school at Columbia!

And here’s the news article, “Ludmerer named distinguished professor in history of medicine.”

In that article, they forgot to mention that Ludmerer is one of the 5 doctors in America who has no opinion on whether cigarette smoking contributes to lung cancer in human beings.

It’s gotta be hard to find a doctor who holds that opinion. Such a man is very special and certainly deserves a distinguished chair. Perhaps he can share it with that doctor who believes that vaccines cause autism, and that other doctor who things that diseases are caused by demonic possession.

There are lots of witches running around in St. Louis. Something must be done!

P.P.S. I’m one to talk, given that I get research funds from Novartis and the U.S. military (for basic research, but still, the military must at some level find it useful to their purposes). Still, no matter how much they pay me, no matter how many awards they give me, I don’t think I’d ever say something as dumb as that I had no opinion on whether cigarette smoking contributes to lung cancer in human beings.

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47 Comments

  1. Tom says:

    I like to think that if I was offered a huge amount of money for giving an opinion that I would take an objective decision which was in line with my moral convictions, but until I am in that highly unlikely position I’ll never know. The vast majority of people will never know how they would act in this sort of situation (unless they know themselves to be amoral from the outset) so I tend to reserve judgement when I hear proclamations to the opposite effect. I’m not really sure that I would like to be placed in that sort of ‘give an amoral opinion and put your kids through university’ position really.

    It doesn’t alter the fact that I wouldn’t want the guy as my doctor either.

    • Rahul says:

      In general, I find the practice of Profs. acting as paid experts on a court case a bit iffy.

      Amicus curae are fine but paid experts seems such a huge conflict of interest that I’m not sure ties in well with the role of a Professor.

      Maybe it would be better if each University had a fixed rate schedule that Profs. could charge for acting as paid experts?
      Otherwise one just shops around till one finds a Prof. willing to be sold I guess. It is only a question of price.

      • Andrew says:

        Rahul:

        Yes, you have a point. I do this sort of paid legal consulting from time to time, and I have been concerned about this selection bias issue. Even if I personally act with full integrity on each case, there is a concern that lawyers can shop around for an expert who agrees with them.

        Part of the point of this post is that I do feel that the Ludmerers of the world should be paying some sort of professional cost for their unethical behavior.

        To put it another way, by testifying, what Ludmerer is doing is trading off his professional reputation to make a ridiculous statement sound reasonable. But it goes both way. Every reaction has an equal and opposite reaction, and Ludmerer’s testimony provides data regarding his general level of competence and ethics.

        • Rahul says:

          Andrew:

          The other side of the story is that the cynics among us assume that everyone who’s a paid expert for a side has essentially sold out. At least a little.

          So you have a bit of a lemon market problem. i.e. Even if you act with full integrity, just because there are so many more who don’t, you will get tarred with the same brush.

          Fundamentally there is this huge asymmetry of information: It is impossible for anyone that does not really know you to decide if you did act with integrity or sold out. All that is manifestly visible is the monetary transaction. And the higher the per hour payments the worse the ethical conflict looks.

          Perhaps over time the most conscientious of the experts just naturally drop out of such a lemon market.

          • Andrew says:

            Rahul:

            Yes, this suggests that it would be better for experts to be hired by the court rather than by the competing parties. But then this is just a special case of the more general controversy regarding the U.S.-style adversary justice system.

            From my perspective, I do some legal consulting because it earns me some $ that I can use to pay more to the Stan team.

            • Rahul says:

              Andrew:

              An adversarial system is ok but nothing demands that Professors be a part of it. i.e. Vigorous representation of their clients is a fundamental duty of lawyers.

              For a Professor, in my opinion, vigorous representation conflicts with the fundamental duty to get at the “truth”.

              A lawyer is not duty bound to broach facts that might reflect adversely on his client’s case. Such partial truth & hurdles to transparency are usually frowned upon in the academic code of conduct.

              PS. I wonder if there have been clergy who acted as paid expert witnesses for a court case. That’d be an interesting conflict of interest too.

              • Jonathan (another one) says:

                As someone who’s been an expert witness for 25 years, the standard corruption story, IMO, has it completely backwards, as Andrew partly alludes to. I know lots of other expert witnesses who I think are idiots and who have positions that make no sense, but I don’t know a single one who adopts his position because of the money. Lawyers indeed shop for someone to espouse the position the lawyers want espoused, but the expert they’re paying (again, in my experience) genuinely believes what he’s saying. The pathway goes from belief to payment, not from payment to belief.

              • Andrew says:

                Jonathan:

                Indeed, to take this one step farther, I suspect that a bit of conviction makes an expert that much more effective. I discussed this awhile ago in the context of a court case where my Columba colleague Glenn Hubbard and I were paid experts on opposite sides. Hubbard’s hourly rate in that case was twice mine, but he may have been worth it, in that, from the quoted deposition transcript, he really seemed to care. He certainly didn’t sound like a hired gun. I came out of reading this transcript with the impression that Hubbard really didn’t think fraudulent mortgage underwriting had been such a problem. And, who knows, maybe he’s right? In any case, I’m speculating that his intense convictions may have made him a more effective courtroom expert, and maybe that’s the case for his expert consulting more generally, maybe he really throws himself into every case 100%: not just his analytical skills, not just his subject-matter knowledge, but his moral convictions.

    • Andrew says:

      Tom:

      Yes, it would be interesting if it were possible to interview this doc and ask him for his rationalization for saying what he said. Also I’m curious what his colleagues at WashU think about him. Do they despise him for saying so amazingly stupid and, I’d say immoral (not just “amoral”)? Do they admire him for all the $ he received? Do they not know he said this? Do they just not care? Or maybe Ludmerer has apologized for the whole thing? I have no idea.

      Does Mark S. Wrighton, chancellor of Washington University in St. Louis, continue to think that “Ken Ludmerer is a tremendous asset to Washington University”?

      And get this: Larry J. Shapiro, MD, executive vice chancellor for medical affairs and dean of the School of Medicine, says, “This professorship will allow Ken to continue to pursue his groundbreaking studies in medical history and education policy as well as continue to teach our students and care for our patients.”

      Would Larry J. Shapiro want this guy as his family doctor? I can just imagine the topic of smoking comes up with a teenage child, and Dr. Ludmerer says that he has no opinion on whether cigarette smoking contributes to the development of lung cancer in human beings.

      It makes you wonder if there’s anything in the world that Ludmerer does have an opinion on. The Denkinger call, perhaps?

      P.S. I assume that a med school prof makes enough $ that he can accord to send his kits to college without having to embarrass himself like he did with that testimony.

      • Alex says:

        I’m not a colleague, but as a Wash U alumnus and former employee I find it embarrassing. Not as embarrassing as this guy (http://www.boston.com/news/education/higher/articles/2010/05/19/professor_dumped_from_oil_spill_team_over_writings/), but still embarrassing. Unfortunately, academic freedom and freedom of speech allow universities to keep embarrassing employees around, especially after tenure. His Wash U page that you linked says that he just (2015) received an award from John Hopkins’ School of Medicine, so presumably he’s providing some service of note.

        • Andrew says:

          Alex:

          Yeah, a quick googling revealed this:

          Dr. Kenneth M. Ludmerer has received the 2015 Distinguished Medical Alumnus Award of the Johns Hopkins University School of Medicine. He received the award for his contributions to medical education, with particular reference to his latest book, “Let Me Heal: The Opportunity to Preserve Excellence in American Medicine,” an account of the residency system in the United States and its relationship to quality of care. Ludmerer is the Mabel Dorn Reeder Distinguished Professor of Medicine and the History of Medicine at Washington University and a member of Congregation Temple Israel. Read the Jewish Light’s 2014 interview with Ludmerer about his book online at bit.ly/ludmerer-book.

          They forgot to mention his career as a tobacco truther.

  2. Jack says:

    Have you ever read the papers proving smoking causes cancer? I have never read them. So although I know most people claim that, I really can’t say if the evidence is any good. So since I don’t take people’s opinion for granted, I would say that I don’t have any opinion on that either, and I don’t smoke because I am lazy to check the evidence and so I am plying save, but it is certainly not because I have knowledge of the evidence regarding this claim.

    • Andrew says:

      Jack:

      I’ve not seen the evidence on the smoking-cancer link or the moon landing, but I have an opinion on both of them.

      I totally wouldn’t want a family doctor who had no opinion on the smoking-cancer link. I don’t know if he’s an idiot, a sleaze, or just an extreme skeptic, but any of these three would represent a problem. As Chesterton said: skepticism, when taken to an extreme, is a form of credulity. I’m a bit more skeptical than Chesterton (or, for that matter, Kahneman) but the general principle applies.

    • Martyn says:

      It’s not even that hard to find the evidence that smoking causes cancer. An expert working group convened by WHO has compiled a report summarizing all the evidence, which you can read online here.

      http://monographs.iarc.fr/ENG/Monographs/vol83/index.php

      The whole thing is 1478 pages, but you can start by reading the summary of data reported and evalution which is just 10 pages. And if you are still skeptical after reading all that then you may be Erhardt Von Grupten Mundt from the movie Thank You for Smoking

      https://www.youtube.com/watch?v=bteUjJnGOwg

      • Anoneuoid says:

        Martyn,

        Thanks for linking there. It is good to have a concrete starting point. I got to figure 1 of your first source and noticed it had no error bars or associated description of methods. They cite Peto et al. (2000), I found that paper, it is a review article also without error bars or description of methods. Those authors (seem to) cite Darby et al. (1998) for “details of the study design and methods of data collection” associated with the figure in question. I am now trying to figure out how exactly they got that graph, which does not appear in Darby et al. (1998). It may come from supplementary table B somehow, but that one does not render properly in either of two browsers (it is covered up by polls/social media junk on the right side and squished together).

        I’m going to complete that task (if possible), but do not want to repeat this for every figure in a 1400 page document. Can you point to the evidence discussed in the IARC monograph you find especially compelling?

    • Anoneuoid says:

      Wouldn’t surprise me if they were wrong about the smoking-cancer thing. Who knows? AFAICT, the medical literature consists of an enormous stream of NHST reports making it impossible to sift the good from the nonsense. The CI push in the 1980s looked promising at first but by and large they have been used only to check if zero was inside/outside.

      I certainly stopped going to the doctor after graduate school in that area. It sounds extreme, but I am more scared of what damage can be done by NHST-confused minds with access to concentrated chemicals and sharp objects than of any disease. It’s easier to destroy something you don’t understand than fix it. Of course, I would go to the emergency room after a car accident, etc. Supportive care seems safe.

      Then again, maybe I should try going back to the doctor. If you’re sick in the jungle, would you prefer to be taken to the witchdoctor or some random person? The witchdoctor probably knows the most about it, that doesn’t mean anything scientific is going on but it may be better than nothing.

      • Martha says:

        I haven’t stopped going to the doctor, but I have cut down on automatically doing what they tell me — I go for a second opinion if it’s something where a specialist might have a more informed opinion than my PCP, and look on the web (but not blindly) to see if what the doctor suggests makes sense (e.g., I may look up the package insert for a prescription before deciding whether or not to fill the prescription — which now seems to require asking for a written prescription rather than having it called in to the pharmacy). And if it’s something that might benefit from physical therapy, I ask for a referral, since my experience is that they sometimes can identify a problem that physicians miss, and that physical therapy can often help prevent recurrences of a problem, whereas taking anti-inflammatories or steroids is just a temporary fix, and typically has side effects that can be as bad as or worse than the original problem.

  3. Paul Alper says:

    A strongly recommended book: “Ending Medical Reversal; Improving Outcomes, Saving Lives” by V.K. Prasad and A.S. Cifu. One of the many themes of this 2015 book is that physicians (as well as statisticians) have vested interests both monetarily and professionally. Not only does the famous phrase of the movie (but not in the book) “All the President’s Men,” “Follow the money” apply, but picture the cognitive dissonance when a medical doctor finds out that his recommended treatment over the years has proved to be worthless/harmful. The appendix of the book lists 146 (!) medical reversals that have taken place from 2001 to 2010. Usually the reversals are due to randomized control trials which overthrow observational data and/or gut-feeling plausibility. One reversal (4/29/04) that might interest the sports-leaning audience of this particular blog is #43 on page 224: “This study argued that the older [open mesh] method for repairing hernias is superior to the newer, [high tech] laparoscopic approach.”

    • Andrew says:

      Paul:

      Did the success of All the President’s Men and The Final Days wreck Carl Bernstein? It’s a classic counterfactual question. Without those successes, would he have had a happy and productive life as a normal journalist? Or would he have drifted into meaninglessness in any case? The $ and celebrity allowed Bernstein to live a fake life, but who knows what his life would’ve been without that shock.

  4. Clyde Schechter says:

    A PubMed search of Dr. Ludmerer’s publications turns up 38 articles. The majority relate to medical education or history. There are a handful of clinical case reports, none since 1996. There are no clinical research articles at all. This is not the profile of a clinician or clinical researcher at a leading academic medical center. Dr. Ludmerer is in a rather special niche. It would not surprise me to learn that he has done no direct patient care since his residency. It would positively astonish me to learn that he has done any since the late 1990’s. So I’m pretty confident he isn’t anybody’s family doctor, and hasn’t been for a long time (if ever).

    It is striking that the tobacco companies would turn to somebody with this history to testify on their behalf. It suggests that they were unable to find a qualified internist, oncologist, pulmonologist, toxicologist, or epidemiologist–somebody with appropriate qualifications–that they could buy off.

    The real problem, I think, is not the occasional oddball who lacks expert credentials and can be paid to say things that are clearly outlandish. Worry more about the influence that money can have on the route that mainstream researchers take when navigating the garden of forking paths. This is a far more insidious problem: the researchers involved will be well respected, and they are likely, themselves, to truly believe their results. Their testimony will be far more difficult to discredit.

  5. Clyde Schechter says:

    Presumably his studies of medical history are considered important contributions to knowledge. He has a joint appointment in the Departments of Medicine and History. There are people like that scattered around Medicine departments across the country. If he can bring in some grant support for his research and perhaps earn some of his keep by doing administrative tasks, it wouldn’t be a strain on the department’s resources to have him. Moreover, it seems he has a named chair. That implies that some donor, presumably somebody interested in supporting his work in the history of medicine, gave an endowment that foots most of the bill.

    • Moreno Klaus says:

      I wonder who that donor is… Isnt it possible that he is somehow connected to this “endorsement”?

      • Rahul says:

        No obvious connection that I could find:

        “Mabel Dorn Reeder (1908-2007) grew up in the small town of McCormick, South Carolina, and was
        passionate about making a better world for future generations. The daughter of a prominent
        businessman and state senator, Mrs. Reeder graduated from Greenville Women’s College and
        attended graduate school at Columbia University in New York. She then taught elementary school for
        several years before marrying Thomas H. Reeder and moving to Atlanta, Georgia, where she lived until
        her death at 98. Today, her passions for music, education, photography, animals, travel, and history are
        carried on through the work of the Mabel Dorn Reeder Foundation.”

  6. D.O. says:

    Re: P.P.S.: Your test will be about statistical (un)certainty that military operations lead to net increase in civilian deaths.

  7. John Mashey says:

    1) To quote something heard often lately “I am not a scientist, but…” might apply to Ludmerer …
    I.e., somebody likley knows what the science says, but can’t say it.

    2) jack: “Have you ever read the papers proving smoking causes cancer? I have never read them.”
    You don’t have to read the original papers, although they are easy enough to find.
    A good strategy is to start at a high level and go only as deep as you need to form an opinion.

    Google: smoking cancer

    a)One of the first-page hits is: Smoking and Cancer at the CDC.
    That has a section “How Is Smoking Related to Cancer?”.

    b)One of the references is to (a somewhat old, 2010) <a href="http://www.cdc.gov/tobacco/data_statistics/sgr/2010/consumer_booklet/index.htm"summary of Surgeon General report
    “This easy-to-read, 20-page booklet summarizes the 700+ page Surgeon General’s report released in December of 2010.”

    c) So maybe this Surgeon General has more info:
    Google: smoking surgeon general
    The first hit there is actually newer and more general:

    d) The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General, 2014.
    That includes a 28MB PDF, 978 pages. Chapter 6, pp/139-352 is on cancer … but of course summarizes the evidence, citing the real paper. There are about *60 pages* of references.

    (Next step takes some knowledge of history):
    Among other papers, the (famous) papers by Richard Doll and (Bradford Hill or Richard Peto or others) were famous long-term statistical studies of British doctors starting in the 1950s.
    For instance, from the SG report:
    “Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation to smoking: 40 years’ observations on male British doctors. British Medical Journal 1994; 309(6959):901–11.
    Google Scholar gets first hit: PDF

    As best as I can tell, good statistical work.
    “After the two large case-control studies of 1950 that
    showed lung cancer to be closely related to smoking,’ 2
    prospective studies were needed that could determine
    which other diseases were also related to the habit. In
    1951 all the doctors in Britain were asked what they
    smoked. Most of the 40000 who replied were male,
    and a prospective study was started of the causes of
    death that subsequently occurred among them.”

    Among other things, Table VII – Mortality by cause… is really importnat.
    People associate lung caner with smoking, in part because it was one of the earliest clearly proven, but often because it has been the focus of lawsuits, since almost nothing else causes lung cancer.
    (Never smoked: 17+17/100,000, current: 264+314/100,000, i.e., large ratio of excess deaths.)
    However, in this study, there were more excess deaths from respiratory and vascular diseases, especially COPD and CVD.
    but it took longer for those to get proved.

    • Anoneuoid says:

      After looking at the papers discussed above and in this post I am baffled by something. Why do they not make a simple plot of lung cancer rates by age (age specific incidence)? Have one curve for non-smokers and one for smokers. The closest is Fig 5, but that is all cause mortality and shows the “excess” rather than the rates.

      Also, check out that table VII again. Current smokers were about ~2x more likely to die of pretty much anything, including trauma and poisoning. Then again, maybe that is an artefact of the standardization:

      “All mortality rates have been standardised for age and calendar period by calculating the number of deaths that would have been expected in each five year age group and each calendar year in each smoking category if the smoking habit had had no effect on mortality, summing the corresponding observed and expected numbers, and multiplying the ratio of the two numbers by the total death rate for the ages and period covered.”

  8. stenglein says:

    Apparently we’re all supposed to be shocked at a medical Doctor’s politically incorrect response to some vague question of cigarettes & cancer. All he said was “I have no opinion on that.” Maybe the Doctor honestly had no definitive medical opinion on that broad topic, or at least not one he wished to share with that questioner under those circumstances.

    The basic origin and cause of cancer is still unknown, even after a half century of intense study around the world. Somewhat like the physical principle of ‘gravity’ — we know a lot about its circumstances & effects, but not its cause.

    The smoking “contribution” to lung cancer rests upon statistical inference, without any definitive biological causation determination thus far. Heavy smokers who never contract lung cancer are not uncommon.

    (and smoking is not physiologically “addictive”; it’s merely a voluntary, nasty habit that’s tough to break )

    • Andrew says:

      Stenglein:

      Sadly, I’m not shocked at Ludmerer’s testimony. People do a lot of unethical things for money. But I do think these sorts of behavior should be aired. If Washington University is cool with its medical school profs going around saying that they have no opinion on the smoking-cancer link, that’s fine, they should be out and proud about it. Why make it such a secret that people have to find out on some obscure blog? They should splash it all over Ludmerer’s webpage, maybe even have him teach a class in the oncology department.

      • Rahul says:

        Andrew:

        Does Columbia University proudly splash Mehmet Oz & his miracle weight-loss supplements on its webpage? How about advertising Sudhir Venkatesh’s taxpayer funded lavish dinners & cab rides for his fiancée to a nail salon?

        All Universities have their black sheep, eh?

        • Andrew says:

          Rahul:

          I’d love it if Columbia were to take more of a stance on Oz and Venkatesh, proudly affirming their support if that’s where they stand on the issues at hand.

          • Rahul says:

            Andrew:

            They already did. Quoting Columbia’s official stand on the Mehmet Oz saga:

            “Columbia is committed to the principle of academic freedom and to upholding faculty members’ freedom of expression for statements they make in public discussion.”

            By this yardstick, I’m sure Washington University is proud to have Ludmerer and his opinions (rather, his lack of opinion) on smoking too.

        • James says:

          I don’t know the background on the Venkatesh accusations you are making, but having worked as a government contractor, I can tell you that the taxpayers do not ever pay for lavish dinners for individuals. There is a per diem and anything above that comes out of your own pocket. That said there have been instances of lavish conferences and meetings being put on towards the end of the fiscal in order to burn end of the year money.

          • Rahul says:

            Background from the NYT Article on this:

            “According to internal documents from that investigation, which were obtained by The New York Times, the auditors said that Professor Venkatesh directed $52,328 to someone without any “documented evidence of work performed.” He listed a dinner for 25 people, relating to research on professional baseball players; auditors found that only 8 people had attended, and that the research project had not been approved.

            He charged Columbia for town cars to take him around, to take his fiancée home from work one late night, to take someone — it is not specified whom — from Professor Venkatesh’s address to a building that houses a nail salon and a psychic. All told, auditors questioned expenses amounting to $241,364.83.

            The documents do not indicate what judgment Columbia administrators reached about the audit, or what actions, if any, they took as a result. Professor Venkatesh said in a brief phone conversation in October that he had repaid $13,000.

            He is no longer affiliated with the Institute for Social and Economic Research and Policy, or Iserp. “

    • Jeff Walker says:

      “basic origin and cause of cancer is still unknown”. We know very well the proximate cause of cancers (note the plural): mutations in cell cycle promotion and checkpoint genes combined with a few other genes that facilitate growth such as those that upregulate glycolysis, or angiogenesis, or the ability to crawl through tissues. Mutations of course are random mistakes in DNA duplication. These occur 24/7/365. You are acquiring mutations somewhere as you read this blog. So ultimately, acquiring a (note that I said “a” and not “the”) combination of mutations that generates a cancerous population of cells is simply bad luck – for everyone – but some things increase your risk of bad luck including the inheritance of some of these mutations and some environmental factors (radiation, smoking) that cause DNA damage (strand breaks, methylation, etc.) and thus increase the risk of mutations.

      “and smoking is not physiologically “addictive”; it’s merely a voluntary, nasty habit that’s tough to break”. This is of course self-contradictory. If it’s tough to break then it’s addictive. I get what you mean by “physiological” but what you mean is the old Cartesian dualism where physiological and mental are two different things. They are not.

      • Anoneuoid says:

        >”We know very well the proximate cause of cancers (note the plural): mutations in cell cycle promotion and checkpoint genes combined with a few other genes that facilitate growth such as those that upregulate glycolysis, or angiogenesis, or the ability to crawl through tissues.”

        I’ve found this explanation does not stand up to scrutiny. It falls apart once you try attaching numbers to it. The theory originated as a quantitative one from Armitage and Doll, but the details have been (supposedly) worked out using largely non-quantitative NHST methods.

        How many mutations are required to accumulate in a single cell, what are the mutation rates? What mutation rate is required to get the observed number of tumors after x years of life? I don’t want to go into details here, but I get answers that differ by ~4 orders of magnitude, mutation rates of normal cells are said to be ~10^-6 per division but rates of near 1/100 are required to explain how commonly cancer is observed. That is even allowing for populations of cells with very high rates of normal division in each tissue (~once each day).

        I am also not aware of anyone who has successfully identified a set of mutations that transforms a cell. The closest I’ve seen is that certain mutations can result in transformed cells many generations later (after genomic instability has had a chance to do who knows what).

    • John Mashey says:

      1) Cancer mechanisms:
      Surgeon General 2014
      Chapter 6 Cancer
      Introduction 143
      Mechanisms of Cancer Induction by Tobacco Smoke 148-

      Some of this takes serious biochemeistry knowledge (more than mine!) to convert to English. Just skip those paragraphs.

      Human variations matter, but a great deal is known, although the complexity of cigarette smoke is always a challenge.
      p.186
      “The evidence is sufficient to conclude that the increased risk of adenocarcinoma of the lung in smokers results from changes in the design and composition of cigarettes since the 1950s.”
      I.e., cigarettes are heavily-designed products that have become more dangerous.

      2) Addiction: search SG for addiction
      pp.30-31
      “The 1988 report of the Surgeon General, also
      released by Surgeon General Koop, reviewed this new evidence
      on smoking and addiction, concluding that: “Cigarettes
      and other forms of tobacco are addicting” (USDHHS
      1988, p. 9) and “Nicotine is the drug in tobacco that causes
      addiction” (p. 9). The third overall conclusion compared
      nicotine addiction to other addicting drugs, including
      heroin and cocaine.
      The report changed the view that smoking was just a
      habit. Cigarettes were now cast as addicting and as equally
      addictive as many illegal drugs.”

      pp.107-138 Nicotine chapter
      Pathophysiology of Nicotine Addiction 112

      =====
      Usage = some mix of physiological addiction and habit (often social).
      It is extremely difficult to get anyone addicted to nicotine outside the period of adolescent brain development, which often stretches into the early 20s (hence, many use the term AYA – adolescent+young adult). This is one of the reasons some people are pushing for a legal age of 21.

      THE cigarette companies have of course known nicotine is addictive for decades and that the AYA period is crucial to getting “replacement smokers.”
      See RJR ~1984, The Importance of Younger Adults.
      3 years late: voila! Joe Camel.

  9. Jazi Zilber says:

    Andrew,

    Are you familiar with stopping smoking effect on lung cancer?

    In short. Seems that lung cancer increases in the first five years after stopping to smoke. But drops sharply afterwards.

    My theory? Stopping to smoke while good is traumatic and causes various changes in the lungs that increases the extant risk for awhile.

    But some went on to argue that this cannot be the cause.
    1) most cancers start many years beforehand. 2) stopping to smoke must be good!

    This junk got published. They theorised that the developing cancer might motivate smoking cessation.

    The error is obvious. While cancers start years in advance. Most of the “developing cancers” most probably never go lethal. So very possibly a systemic change a year before detection might be the tipping factor.

    Might find the references if curious….

    • Rahul says:

      Could this be a co-morbidity effect? i.e. People give up smoking when they notice non-cancer but smoking-related symptoms or are diagnosed with say COPD or bronchitis.

      Any way to test this hypothesis?

      • Jazi Zilber says:

        Here is the paper of elevated risk.

        http://www.medical-hypotheses.com/article/S0306-9877(05)00170-2/abstract

        Elevated lung cancer risk shortly after smoking cessation: Is it due to a reduction of endotoxin exposure?

        Summary

        Several reports indicate that the risk of lung cancer increases slightly for a short period of time after cessation of smoking while the risk of adverse cardiovascular events drops immediately. Recent studies on subjects occupationally exposed to organic dust-containing endotoxin have revealed lower than expected rates of lung cancer. There is experimental evidence that stimulation of the immune system by endotoxin has a protective effect against cancer. Tobacco smoke has been shown to contain high levels of endotoxin. We therefore postulate that cessation of smoking eliminates the protective effect of endotoxin. Any benefit conferred by endotoxin does not, however, justify smoking. As the inverse relationship between exposure to endotoxin and the risk of lung cancer is a strong one, endotoxin-like substances could form the basis of vaccination strategies

      • Jazi Zilber says:

        Testing will be tough. As the info currently is sketchy, several studies, but all epidemiological.

        Lots of data collection will be needed

    • Anoneuoid says:

      I’m not sure why this is surprising. It is consistent with the multi-stage model. According to that idea, the way carcinogenesis works is accumulating “changes” of some kind in a single cell, usually assumed to be somatic mutations, and these occur primarily during cell division. Then you would expect detection of tumors in a tissue to be some lagged function of the cell division rate. Breathing smoke would be damaging the lung tissue, necessitating extra cell division to generate replacement cells.

      However, the tissue is never really able to heal fully because there is all that crap built up around the cells. Once the person stops breathing in smoke, the crap gets cleared away and the cells can fill that space with new tissue. Thus, for a short time, the division rate increases to even higher than during the smoking phase. I’m not sure why people are invoking endotoxins, etc. A perfectly fine explanation falls right out of the theory of accumulating mutations. Has anyone measured division rates of various cells exposed or not to smoke in lung tissue to check this?

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