How we know that cigarettes cause lung cancer and vaccines DON’T cause autism

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Even those who can’t tell the difference between a t-test and a chi-square are familiar with a basic principle of epidemiology: correlation does not equal causation. Just because Event A happened before Disease B, it does not mean that A caused B.

For example, in last 100 years deaths from infectious diseases has declined precipitously. During the same time span, the recreational use of marijuana has also increased. Yet no one would suggest that the decline in infectious disease deaths was caused by smoking marijuana.

One experiment or even a few experiments is not enough to determine causation.

So if correlation does not equal causation, what does?

To determine if Event A caused Disease B, we need to investigate whether it satisfies Hill’s Criteria. These are 9 criteria, most of which much be satisfied before we can conclude that Event A is not merely correlated with Disease B, but Event A actually causes Disease B.

Who was Hill and why should we care about his criteria?

… These criteria were originally presented by Austin Bradford Hill (1897-1991), a British medical statistician as a way of determining the causal link between a specific factor (e.g., cigarette smoking) and a disease (such as emphysema or lung cancer)… [T]he principles set forth by Hill form the basis of evaluation used in all modern scientific research… Hill’s Criteria simply provides an additional valuable measure by which to evaluate the many theories and explanations proposed within the social sciences.

What are the criteria?
1. Temporal relationship: It may sound obvious, but if Event A causes Disease B, Event A must occur before Disease B. If smoking causes lung cancer than smoking must precede the development of lung cancer. The is the only absolutely essential criterion, but it is NOT sufficient. Lay people often erroneously assume that because it’s the only essential criterion, it is the only criterion that counts. For example, anti-vaccine parents often point to the fact that childhood vaccinations usually occur before the onset of autism, but that does not mean that vaccination causes autism. Learning to walk usually precedes autism, too, but obviously learning to walk does not cause autism.

2. Strength: This is measured by statistical tests, but can be thought of as similar to the closeness of the relationship. Is Disease B always preceded by Event A? Sometimes? Only rarely? Does Event A always cause Disease B? Sometimes? Only rarely? Lung cancer is not always preceded by cigarette smoking, but it usually is. Cigarette smoking does not always lead to lung cancer, but it often leads to lung cancer. In other words, the relationship is fairly strong.

In the case of vaccines and autism, vaccines usually precede the diagnosis. However, most children who receive vaccines don’t develop autism. Thus the relationship is weaker.

3. Dose-response relationship: If cigarette smoking causes lung cancer, we would expect that smoking more cigarettes would increase the risk of lung cancer, which it does. In contrast, there appears to be no dose-response relationship between the number of vaccinations and the risk of developing autism.

4. Consistency: Have the findings that purported to show a relationship been replicated by other scientists, in other populations and at other times? If studies fail to consistently show the relationship, causation is very unlikely.

This is a critical point. One experiment or even a few experiments is NOT enough to determine causation. A large number of experiments that consistently show the same result is required; that’s exactly what we find in the case of cigarettes and lung cancer. This is particularly important for anti-vaxxers to note. The fact that a few studies claim to have shown that vaccination causes autism is meaningless when a very high proportion of studies show that there is not even a correlation between vaccination and autism.

5. Plausibility: In order to claim causation, you MUST offer a plausible mechanism. In the case of cigarette smoking, certain components of the smoke are known to cause damage to the cells inside the lungs, and cellular damage has been shown to lead to cancer. In contrast, no one has yet offered a plausible explanation for how vaccines “cause” autism. In fact, no one can even agree on the specific component that is supposedly responsible.

6. Consideration of alternative explanations: This is self explanatory. In the case of vaccination and autism, there is a very simple alternative explanation. Autism cannot be diagnosed before the age of 2 and most vaccines are given before the age of 2.

7. Experiment: If you alter Event A do you still get Disease B. In the case of smoking, if you quite smoking, the risk of lung cancer goes down. In the case of vaccines and autism, if you forgo vaccination, the risk of autism remains unchanged.

8. Specificity: Is Event A the only thing that leads to Disease B? This is the least important of the criterion. If it is present, it is a very powerful indicator of causation. For example, among young women who developed a rare form of vaginal cancer, all of them were found to have been exposed to DES (diethylstilbestrol) while in utero. That is a highly specific effect.

However, even if the relationship is not highly specific, that does not preclude causation. Though there are non-smokers who get lung cancer, it does not change the fact that the other criteria show that smoking causes lung cancer.

9. Coherence: The explanation of action must comport with the known laws of science. If the purported mechanism of causation violates the law of gravity, for example, then it isn’t acceptable. That’s why religious arguments against evolution are wrong. They are “incoherent” since they invoke forces outside science.

What do Hill’s criteria look like in action?

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In the case of cigarette smoking and lung cancer, 8 out of 9 Hill’s Criteria are satisfied. In contrast, in the case of vaccines and autism, only 2, possibly 3 criteria are satisfied. This is why we can say that the scientific evidence shows that vaccines do not cause autism.

While it is true that vaccinations usually precede the diagnosis of autism, that is an essential criterion, but not enough. The fact that there is no dose-response relationship, that the few studies that showed a purported relationship cannot be replicated and that studies in which people who were not vaccinated did not have a lower incidence of autism, demonstrates that vaccines do not cause autism.

  • The Computer Ate My Nym

    Re autism and vaccination and the proposed mechanism, given that autism is almost certainly a set of phenotypes produced by multiple different triggers, possibly including both genetic and environmental factors, I could imagine that inflammation might provoke or worsen autism in some cases. And vaccines can cause an inflammatory response, though not as severe as that of getting the actual disease. So there could be a plausible mechanism by which vaccines could cause autism. Except that if the minor inflammatory response of a vaccine is going to cause autism in that individual, it’s hopeless: even if they aren’t vaccinated AND somehow manage to avoid getting any VPD, they’ll just become autistic the first time they get a cold or maybe with teething. So might as well vaccinate, even if it is true. (Which, I should add, is complete and utter speculation on my part.)

  • The Computer Ate My Nym

    I would actually put specificity as a +/- rather than a flat out no for smoking. Smokers are far more likely to get lung cancer than non-smokers and are more likely to get specific histologies (most strongly small cell lung cancer, which is extremely rare in non-smokers). Furthermore, there are differences in the cancers non-smokers get versus those that smokers get. Non-smokers are more likely to have adenos and more likely to have specific mutations such as EGFR and ALK. That all suggests a specific effect, a bit obscured because there are also non-specific effects going on at the same time causing a similar disease.

  • Sue

    If anyone has lingering doubts about the nature of Wakefield’s “study” of twelve children, it’s worth reading the detail of what he actually did. Here is the evidence compiled by investigative journalist Brian Deer, which defeated Wakefield’s SLAPP motion against him.

    http://briandeer.com/solved/slapp-amended-declaration.pdf

  • Squirrelly

    Maybe I am confused but shouldn’t specificity for vaccines/autism be a no? I would imagine you can find non vaccinated autistic people, hence vaccines could not be the only event leading to autism.

    • Amy Tuteur, MD

      Oops! I fixed it.

  • Megan

    OT but hoping for some personal experiences and/or expert opinions: My daughter has a cow’s milk allergy that was diagnosed at 2 weeks of age after I switched to EFF of dairy formula. She had severe GERD and hives with every bottle. We switched to Alimentum and the hives resolved completely while the GERD had the usual waxing and waning course with a big improvement around 3.5 months of age which I suspect was just growing out of the worst of it. She still is a spitter mind you, but no more projectile vomiting entire bottles of formula a la “The Exorcist.” At her 4 month visit we discussed the possibility of re-introducing dairy. Our doc said we could try with a small amount of formula, say one ounce, and see how it went. I tried finding professional resources on this at work but couldn’t find much other than the usual info that most kids do outgrow their dairy allergies (I had one as a child and I outgrew mine). I did find something from the NHS as far as a “ladder” for reintroducing dairy foods but they suggest reintroducing at 9-12 months. So, anyone have any stories about their CMPI babies or any suggestions as to when/how to proceed? I’d love to save money on formula but obviously don’t want to make my daughter miserable again. Perhaps I’d be better off with trialing yogurt and/or cheese before formula?

    • Heidi

      I don’t know that Similac has a version of it, but Enfamil has Gentlease and the protein are only partially hydrolyzed. I imagine it’s a bit cheaper. I wonder if that would make transition easier?

      • Amy M

        Similac does, or at least did, when my children were babies. I think it was just called Similac Sensitive

    • Bombshellrisa

      Similac has a sensitive formula, maybe that will work for little lady?

      • Megan

        Well, I had bought formula before he was born and wanted to use it so I didn’t waste my money but I guess that is an idea… Maybe we’ll give her an ounce of what we have this weekend and see what happens. Worst case, I guess she gets hives and we switch back again. It’s just frustrating how little specific guidance there is on this aside from one NHS document (that I could find).

    • Allie

      I wonder if the reaction was a true allergy, or just a reaction to something that was too rich for her. My LO had a skin reaction (red splotchy rash) to berry syrup (I think it was Saskatoonberry) when she was around 7 or 8 months. She has had berries and berry syrup since without incident. I think it was just too rich for her system. She had a similar reaction after 6 days on Amoxicillin, and they basically told us they have no idea or way to tell if she has a true allergy to penicillin or if it was just a viral rash. I guess we’ll avoid penicillin (and antibiotics in general, of course, unless absolutely necessary). As for the GERD, we struggled with wicked spitting up. It seemed like she spit up the whole of every feed until she was 7 or 8 months (the allegedly precious and infallible breast milk, no less). I had just about given up on her ever wearing anything nice. I remember one day she went through 11 t-shirts in the course of just the daytime (not counting overnight). Thankfully, that improved suddenly and markedly : )

    • Inmara

      I can offer only anecdotal stories from acquaintances and most of them said that soonest when children outgrew cow milk and egg allergies was after 1 year of age, but mostly later, around 4-5. My baby is almost 1 and still develops dry patches on legs if I give him a bit of cow milk products or eggs.

    • Dr Kitty

      The advice in the UK for CMPI is indeed to avoid dairy until 9-12 months.
      Most of them outgrow it by 18 months, but re-challenging repeatedly before the child has outgrown the intolerance is thought likely to prolong resolution and cause symptoms that will make the baby miserable. Very few will have outgrown it before 9 months.

      Thickeners like alginate (Gaviscon) or Carob seed flour (Carobel) work pretty well for reflux, failing that ranitidine or omeprazole will often do the job.

      If cost is the main concern, a less extensively hydrolysed formula or a goat milk formula might be options.

      Yogurt and cheese are no good- the allergy is to the protein in the milk, not lactose (lactose intolerant people often tolerate fermented milk products better than straight milk, people with CMPI don’t).

      I have an adult relative with CMPI who can tolerate sheep and goat milk and cheese, but the chance of cross reactivity are high and that is not common.

      • Megan

        Thank you! I only even mentioned yogurt and cheese because they are lower on the NHS “ladder” than the actual formula, which is what our doc suggested trialing. I guess I could give a partially hydrolyzed formula a try. I was just trying to use the formula that I had bought in advance of baby’s arrival. I hate to waste it! Obviously though, her comfort is of the most importance. I was a bit skeptical that she would have outgrown a Ig-E mediated dairy allergy at this young of an age and wasn’t sure if it was worth trying at all. I’m pretty sure as a child I continued to get hives from dairy until I was over at least age 1. Perhaps we should just keep doing what we’re doing.

        • Megan

          Oh and forgot to mention, we had her on Zantac for a few months and I missed a few doses because of an insurance issue and found that it was making absolutely no difference. Thickening with cereal didn’t help either, in fact made it worse. Eventually it just improved on its own (as it usually does) around 3.5 months so now she’s not on anything for it.

    • SporkParade

      Is CMPI the same thing as MSPI? Because, if not, we might be talking about two different kinds of allergies here. If it’s just a gastrointestinal allergy, then yes, in my experience, they do tolerate more highly processed dairy products, like cheese and yogurt, before they tolerate liquid dairy, and the recommendation is to wait until 9 months at a minimum for attempting to reintroduce dairy. If, however, we’re talking a regular food allergy, which we might be due to hives, I don’t have any useful information for you.

  • Irène Delse

    Dr. Amy, doesn’t the table at the end have a glitch? “Plausibility: Yes” for vaccines and autism. But the text explains (correctly, IMO) that the anti vaccine crowd don’t even agree on an mechanism.

    • Monkey Professor for a Head

      I’m not sure why specificity says yes for vaccines/autism either.

      • Christopher Hickie

        I agree. I think plausibility should be a “no” for the “vaccines and autism” column based on the lack of any one coherent mechanism being offered by the “vaccines cause autism” crowd.

    • AlisonCummins

      Yes, the text says “5. Plausibility: In order to claim causation, you MUST offer a plausible mechanism. … [N]o one has yet offered a plausible explanation for how vaccines “cause” autism. In fact, no one can even agree on the specific component that is supposedly responsible.”

      But the chart shows plausibility, which appears to be an error.

  • Clorinda

    Mistaking correlation and causation is what makes some of the fake diseases that are getting popular (like chronic lyme, adrenal fatigue, candida overgrowth) so compelling to people. You’ve been tired ever since X event? It’s got to be undiagnosed Y. Try my supplement/treatment and you will be cured! But people forget that X event also coincided with W, M and B. People want answers now. But it can take time to eliminate possibilities.

    • Sue

      Yes – this is a prominent feature of the Woomeister, providing “alternative” health care – give every symptom a false but firm diagnosis ->sell a remedy.

      As medicine has become less paternalistic, the woomeisters, the New Paternalists, have rushed in to fill the void. The woo industry is raking in the $$ with simplistic answers and products.

  • AirPlant

    So is this where we talk about the gloriously implausible mechanisms that we have heard is support of team natural?
    Because the magic boob sensors that detect illness, age, and general condition of the child remain my favorite.

    • Megan

      “magic boob sensors”
      I feel like my husband might have those… Not what you meant? OK sorry. 😉

      • DelphiniumFalcon

        Only if they’re the kind that sense when a boob is unclothed no matter the vicinity or walls seperating you in the house. That is some black magic right there lol.

        • Megan

          Yup.

        • BeatriceC

          That’s the kind mine has. It’s like a guided freaking missle. My shirt and bra come off and MrC appears out of nowhere.