No free hook: science gets it right about smoking

Well, the last nail may have been hammered into the smoking coffin.  Over the years each form of indulgence has been advocated by those hoping to escape the normal health evils of tobacco.  No cigarettes?  Just chew!  No chewing? Just snuff it!  No snuffing?  Just go to a hookah parlor and enjoy the aromatic herb via glass tubes!

Well, the latest news is that even hookahs, while cooling the smoke, do not remove the nasty harmful chemicals.  That's too bad, but in a way it is a triumph for science.  Even famous--the most famous--geneticists have occasionally worked for the Tobacco Institute attempting to debunk the overwhelming data on smoking's dangers (see work by our colleague, historian Robert Proctor, who has battled Big Smoke for years to expose their disingenuous claims to safety).

RA Fisher, one of the developers of population genetics, statistics, and evolutionary genetics once claimed that there was no evidence against tobacco.  This was one of the most infamous instances of someone who had somehow been bought, hoodwinked, or in some other way made themselves believe that the evil weed wasn't.

The ingredients in tobacco satisfied the major criteria for cancer causation: they include mutagens that attack DNA.  That's why, for example, it is oral and lung cancers that are the main cancer risks of smoking.  The exposed tissue experiences somatic (as opposed to inherited) mutation, that transforms some unlucky cell into a tumor progenitor.  Other diseases--the majority of smoking-related diseases in fact!--affect various tissues, like the heart, via other biological mechanisms.  And smoking is correlated with other behaviors like heavy drinking that have their own health risks.  Thus, mechanisms follow what one would expect.

There may be some people who inherit genotypes that make them more vulnerable to these effects--that is mutations that, on their own, are only partial cell transformers, so that smoking only has to cause a few more before a tumor cell is generated.

But overall, smoking shows in many ways how risk mechanisms, including natural variation in the population, can be genetic and real even if indirect or multiple in nature.  In the case of smoking-related diseases, unlike many others, the risks are high and common enough that we can work many of them out.

So, it's time to get off the tobacco hook, for anyone who still doubts.  Unfortunately, many students, amazingly, still smoke even though they know the awful truth.

When science gets it right: a smokin' prediction

Science, as practiced by scientists, has lots of flaws and fallibilities.  Methods and inertia and vested interests sometimes drive what's done and how it's done.  When inappropriate designs or methods are used to answer a question, or when an idea (or belief) is so strong that it can hardly be falsified by scientific evidence, science deserves criticism.

But when science gets it right and for the right reasons, this should be recognized as demonstrating that causation does actually occur in this world and can be identified when the situation is clear enough, by the methods we know how to use.  Often, success comes when a single cause is strong on its own, and predictive of an effect.

There have been decades of very good evidence that smoking causes lung cancer.  One can predict that a certain amount of smoking should lead to a certain amount of cancer.  It's not precise, but it's clear, and shows, at least statistically (since not even most smokers get lung cancer), that smoking is a causative agent.  Given what we knew of male smokers and cancer rates decades ago, information gathered when most smokers were males, it was predictable that when women started thinking that a smoke was cool they'd start joining their men friends in the cancer wards.

Women began smoking in large numbers around 25-50 or more years ago, and a new study demonstrates that it's catching up to them.  Also reinforcing the causal connection, men had quit smoking in large numbers at about the same time in the past, and their rates of lung cancer have been declining as would have been--as was--predicted.

Lung cancer rates have more than doubled for women over 60 since the mid-1970s, figures show.

Cancer Research UK figures say the rate rose from 88 per 100,000 in 1975 to 190 per 100,000 in 2008, the latest year for which statistics are available.

Lung cancers in men fell, and CRUK say this is linked to smoking rates.

The proportion of male smokers peaked before 1960. But women had rising rates in the 1960s and 1970s, which would have an effect on those now over 60.

Overall, the number of women diagnosed with lung cancer has risen from around 7,800 cases in 1975 to more than 17,500 in 2008.

Figures for men went from 23,400 over-60s diagnosed in 1975, falling to 19,400 in 2008, with rates showing a similar large drop.

Strong evidence, to go with laboratory and molecular/biochemical evidence about the nasty ingredients in smoke and what it does to DNA to transform nice, pink healthy lung cells to charred, ugly cancerous one (anybody who's taken a gross anatomy class in a medical school has probably seen the coal-bag lungs of cadavers of former smokers).

Famous people, most notoriously RA Fisher, one of the founders of modern statistics, have tried to find reasons why this association was due to confounding--some true cause other than Virginia's finest, but that was correlated with smoking. But the evidence has piled up the other way (despite the effects of other exposures).

Other predictions
So this is prediction about the future made from past observations.  But what about the other kind of prediction?  A scientific theory can be really convincing if it can make some additional predictions that would be a consequence of the hypothesis.  So, what if you go not to smokers and non-smokers and follow their exposure rates, but go to lung cancer wards and ask whether the patients were smokers? You'd expect to find that most of them were, and that is what the evidence shows.  Even with twists, such as in Utah, where the population is heavily Mormon.  Mormons don't believe in smoking, but the cancer wards in Utah suggest that Mormon lung cancer patients had apparently not adhered to their religion's teaching.

Understandably, attention is on the gruesome outcome of lung cancer.  But we can make another prediction, and we guess some of the data are probably already in hand.  In many studies, perhaps largely of men since they were the main smokers, a high fraction of smoking-attributed death and disease was not due to lung cancer, but involved many other systems--heart attack, emphysema, and many others.  Lung cancer is only a minority, perhaps a small minority of these consequences.  So we can predict that these traits have diminished in men (we think they have), but should be increasing, along with lung cancer, in women.  If that turns out not to be the case, then we have to revisit much that we think we know about smoking.

Given both the prospective prediction and retrospective assessment, our ideas about cause and effect receive strong, persuasive scientific support.  No weakling GWAS evidence here!  Yet, why given this strong and clear support for smoking as a sledge-hammer kind of risk factor, do so many people--even college students who learn about these facts in a reasonably rigorous way, still smoke?  It raises questions about the efficacy of education, about understanding of statistics and risk, and of the impact (or not) of scientific knowledge.

Because today, only the tobacco industry would still claim that smoking was just plain innocent fun.

Huff and puff away!

For years when giving talks about the problems in identifying genetic causation, in QandA time Ken has often been asked, "Well, if things like GWAS aren't really working, then tell us what to do instead!" It's spoken as a dare, but that's entirely off the mark. Just because someone explains that a given approach is not very effective and why does not mean they are obliged to suggest a new miracle theory or cure. In practice, science is part of society and won't--or can't--make major gear changes without a new path to funds, jobs, and so on.

Another statement made in frustration by audience members is, "I want a pill for lung cancer, so I can continue to smoke!". That's not only a dream, but a subtle reason why even genetics, if perfectly successful, will not solve the disease problem as promised.

But smokers, take heart! And you won't need to get your genes diagnosed by the carnival barkers at direct-to-consumer companies. In fact, you can smoke away with much less risk, almost enough to be worth it (if you smoke a tasty brand). "Nuts!" you say, knowing in your heart that smoking's a killer no matter what. But thanks to another public service study, we can say "That's right!".

Because the study says that consumption of B vitamins, and nutrients like, yes, nuts can cut your risk of lung cancer in half, even for smokers.

So why have we wasted so much research money, that taxpayers could have used to buy their smokes and peanuts? Because it's good for the science business? Because nobody had any reason to think that vit B could have anything to do with lung cancer? We don't know the answer, but in a technophilic society we think technology first and simple answers second. And we have to echo Tuesday's post, too: this study is probably at least as likely to be due to unobserved confounders than the vitamin itself.

Sadly, we have to close on a downer note. The majority, perhaps the vast majority, of smoking-related deaths are due to diseases other than lung cancer, not to mention quality-of-life effects like blindness and years of emphysema. So, put the pack away for a rainy day. But keep the nuts, because they could be good for you for other reasons--unless confounding erases the effect!