Polonium-210 in tobacco contributes to many of the cases of lung cancer worldwide. Most of this polonium is derived from lead-210 deposited on tobacco leaves from the atmosphere; the lead-210 is a product of radon-222 gas, much of which appears to originate from the decay of radium-226 from fertilizers applied to the tobacco soils.
That's an interesting question because it's the first time I hear about radium in artificial fertilizers. Will need to dig into these Wikipedia sources.
That tobacco contains lead and polonium had been known for decades, but I used to think that it originated from the decay of natural atmospheric radon and these plants just had some unusual tendency to accumulate heavy metals.
Maybe I should put my tinfoil hat on and run away from non-organic food too?
edit:
From the first source:
Tobacco farmers in developed countries primarily use manufactured fertilizer high in phosphates produced from apatite rock that contains radium-226 and descendant radioisotopes such as lead-210 and PO-210. Tobacco is a unique agricultural crop in that its flavor depends on nitrogen reduction, which occurs through the repeated application of high-phosphate fertilizers. The higher the phosphate level of the fertilizer, the higher the concentration of PO-210 in the tobacco plant. Tobacco grown in certain developing countries has approximately one third less radioactivity than tobacco grown in developed countries, and the radioactivity of tobacco grown in the United States has increased over time.
The safest way possible to smoke tobacco is to grow it yourself.
The small yields will limit you to smoking only a few time a month.
You will want to taste that homegrown tobacco so you will most likely invest in a good old wooden pipe. This will make it so that you don't inhale the smoke into your lungs.
You will however still be at risk of mouth and throat cancer.
So the "you don't inhale it" part of that has absolutely nothing to do with the properties of the pipe/cigar. You can easily inhale on both and you can also choose not to inhale with a cigarette.
You can with a cigarette but it won't be any fun. Pipe enthusiasts will pay premium to smoke different blends of tobacco. It's all about the taste, the quality of the smoke and the ability to sit in a rocking chair and relax.
The best comparaison would be downing a shot of jager bomb vs. a nice glass of single malt whiskey that you will sip for an hour.
No need. Nicotine is absorbed by the soft tissues of the mouth. Inhaling prevents you from "correctly" smoking a pipe.
Take a look at this (formatting mine):
"The Breath Smoking Technique
It requires a relaxed setting, preferably sedentary and a very slow and calm breathing pattern.
The pipe bit is held to the lips continuously and all breathing is through the nose.
Every 2nd or 3rd slow breath through the nose, a tiny puff is taken through the stem, held in the mouth and slowly, very slowly, discharged back through the stem, raising but the faintest wisp of smoke from the top of the tobacco bowl, and then re-drawn back through the stem.
One does NOT inhale the smoke, but if one gets very good at it, one does not even have to puff: the slight vacuum created in the mouth by nose breathing will draw the finest of puffs through the stem.
The blowing back through the stem is alternated with regular, but very slight puffs so that the whole process of smoking seems as natural, regular and effortless as breathing.
I'm sure many smokers have discovered this technique, or variations of it, on their own.
The advantages are that mastering it will produce the coolest and most flavorful smoke possible, and the slow regular breathing will invoke the calmness and clarity of mind to perceive the results at their fullest."
There's a risk from radioactive elements in the tobacco, from the air which in turn is from the fertilizer used. Maybe growing it yourself doesn't change this risk?
It would be if marijuana were grown in open fields and fertized by crop dusters. As of right now most weed is fertilized by hand so the fertilizer doesn't get on the flowers.
The next link is the first source for the Wikipedia paragraph I originally quoted. They say that somebody found about half of the polonium contained in tobacco to be inside of the leaves.
Naturally-occurring? Bananas have radioactive potassium for instance. Somehow the biological process (banana plant/animal digestion) must concentrate it.
The banana plant extracts potassium from the soil and deposits it in the banana, but it doesn't do anything to change the isotopic ratio, the makeup of the potassium in the banana will match the makeup of the potassium in the soil.
The plant might put a higher percentage of potassium in the fruit than exists in the soil, or it might not. So it isn't clear if it concentrates it (it certainly makes it more appealing to consume it).
This has some legal implications. You can now prove fairly conclusively that your lung cancer came from smoking. I wonder if it will lead to a new wave of tobacco litigation.
Smokers were already and for a long time aware of the risks. They choose to take them. What could they possibly claim? That a product known for causing lung cancer caused lung cancer?
That's a good point, I am not a lawyer so I can't really comment. But perhaps there is a material difference between saying you developed a disease that could have been caused by smoking (as lung cancer occurs in non-smokers), and saying you were definitely harmed by smoking.
Other avenues could be:
- Smoking is also associated with other cancers, such as esophageal cancer and bladder cancer. Generally the warnings don't mention this however. By examining the mutation patterns in an esophageal cancer, you could relate it more conclusively to smoking, and could therefore claim you were not warned about that specific risk.
- Tissue samples from lung cancers diagnosed 20 or 30 years ago are sitting in archival storage. You could sequence the whole genome or exome of these tumours for about $1000 - $2000. Statute of limitations aside, sequencing these tumours could reveal the tobacco signature as a basis for a claim from a time when it was less clear or less public what the risks were.
- Passive smokers could have a case if their cancer shows a tobacco signature.
I don't see how you can prove particular mutations are tobacco related. DNA can be damaged by viruses, solar radiation, various industrial chemicals, and naturally occurring replication errors. How would you prove this particular mutation was the result of smoking?
I don't see how this research changes anything from a legal perspective. We already knew smoking causes genetic mutations, but we also know people who've never been exposed to tobacco can develop lung cancer.
The aim is to prove that the pattern of mutations in the tumour (which typically contains several hundred mutations in coding regions, more in the whole genome) are caused by smoking.
Lung cancer is caused by smoking 85-90% of the time. Probably more if you add in secondhand smoke. I think it already meets any sort of "preponderance of evidence" sort of bar to just assume anyone with lung cancer got it from smoking.
Suppose that I live in an apartment with a wood stove, second-hand smoke from a room mate, and radon. If I get lung cancer, which one is to blame? How do you know?
They could easily claim that a product which would otherwise would not have these risks was made into a risky product by the use of certain carcinogens present in the pesticides. The choice of pesticide is made by the tobacco company, so it is their actions that introduce the carcinogen into the product.
Seems pretty standard to me, and I would have to guess that this is the kind of lawsuit that you would probably support if the product in question was, say, red meat instead of tobacco.
I think that in all other areas it's been on the manufacturer of products to make them safer over time (cars, children's toys, cosmetics etc.) so shouldn't the tobacco companies be trying to make their product safer?
Not all other areas. Some products are inherently unsafe, and that is precisely what the costumers want. Alcoholic beverages are unsafe, even lethal if you drink too much. They could be made safer by removing the alcohol, but that is not what most people want. The same applies to fast food and sugary drinks: could be made much safer, but people want a certain flavor at a certain price (and most know it's not healthy).
Inhaling the smoke of burning tobacco leaves can cause cancer. I am fairly certain nobody has as strong of an incentive to create cancer-free tobacco as tobacco companies do. That does not mean it is possible, right?
"Some products are inherently unsafe, and that is precisely what the costumers want."
Radioactive material in tobacco might be mutually exclusive from nicotine and MAOI content. My layperson guess is getting rid of the radioactivity would require prohibitively expensive hydroponic growing. It's the drug part that consumers want, and I'm pretty sure if given the knowledge and option they'd go for non-radioactive cigarettes.
Swedish snus is made to minimize tobacco-specific nitrosamines (TSNAs), but seems to not address Polonium-210 on account of the radioactive stuff being "comparable to that from the natural background radiation sources or dental x-rays": https://harmreductionjournal.biomedcentral.com/articles/10.1...
That excuse doesn't seem to hold up to scrutiny. Who really wants to have 10-20 chest x-rays done per day? Are "dental" x-rays really as weak as "background" radiation?
Alcohol seems to be in a similar position - see the popularity of nice wine and beer over e.g. guzzling cheap spirits.
I think people want health AND pleasure, and are willing to do their own hedonic calculus.
My point is that reality limits how much safer you could make a product. Would it be nice for cigarette or alcoholic beverages to be safer? Yes. Is it possible? Apparently not.
Either tobacco becomes a controlled substance (I am deeply opposed to this given the catastrophic social consequences of prohibition in general), or adults behave like adults, understand the risks, decide for themselves and accept the consequences. Maybe it's because I'm European, but anything else sounds like insanity to me.
By the way, I am not being judgemental in any way. I am an ex-smoker and I drink socially. If people want to smoke (without polluting the environment of others who don't) it's their right, and I completely understand. I used to love it too.
What on earth are you talking about? Tobacco is already a controlled substance in more ways than nearly anything that you can buy at a store (including guns).
I meant prohibited, of course. I think that is fairly obvious from the context of my post. Sorry for the lack of rigor.
Where I live it is almost impossible to buy a gun. On the other hand, I can go downstairs and buy a pack of cigarettes with the same ease that I could buy bubble gum. No questions asked, no ID needed, no records.
It is possible to make them less carcinogenic. Carcinogens come from fertilizers and pesticides (which could be controlled/replaced), from the curing process (which could be replaced with anaerobic curing), and from additives (which could not be added). So a lot could be removed, but there is still inherent bad stuff in breathing smoke. That's enough to cause blowback from people who are afraid that advertising "safer cigarettes" would encourage more people to smoke. Lengthy expensive IP/patent lawsuits have also delayed development. And of course there's the issue of whether customers like it, whether it's profitable, and how much it cannibalizes the tobacco company's other business.
Possible to improve? Yes, perhaps significantly. Economically and politically feasible? Maybe not so much.
I'm not sure that this could prove that. I believe that the mutation rate for non-smokers that develop lung cancer should be elevated as well. Perhaps there is a statistical difference, but it might not be easy to prove with certainty.
Very interesting, does look promising indeed. However, currently it still seems unclear that they have enough data to say with certainty that these "signatures" are unique or complete.
From your source:
> With more cancer genome sequences and the additional statistical power this will bring, new signatures may be found, the profiles of current signatures may be further refined, signatures may split into component signatures and signatures may be found in cancer types in which they are currently not detected.
These signatures will never be unique or complete. Remind you that this is biology where there is not the TRUTH to be found. At some point you can always subdivide one phenomenon in to two cases.
These signatures are generated from non-negative matrix factorization which generates signature vectors more or less stable depending on the amount of input datasets and the number of signatures you want to obtain. And at some point you are limited by the amount of money you have for these dataset (still more than $1000 per patient) and how many patients exist in the end (there may be correlations we will never get to know because the search space is much bigger than the 7 billion people we are can provide in correlations.
You leave out the fact that there is a known carcinogenic mechanism for smoking, and this corresponds to the signature derived by NMF. In vitro studies in controlled systems exposed to smoking carcinogens also reproduce this signature. In addition to the NMF signature, there are other features like transcriptional strand bias, and dinucleotide substitutions. This is a bit more than an association.
Hitting yourself repeatedly over the head with a hammer can give you a headache. Not sure DeWalt are worried from a litigious point of view. I doubt there is a smoker alive today who can reasonably claim to have been unaware of the risks when they started.
Anal point - why the apostrophe? Should it be "Smoking becauses hundreds..."?
I'm an ex-smoker and I had the same thought as I read the article: I wish I'd known this.
But really, I know it wouldn't have made a difference. From an early age I was taught at school that smoking would kill me and I started anyway. The idea that detailed knowledge of one particular cause of death would have made a difference is laughable. It's just a way of deflecting blame from one's own responsibility.
I dunno, there's a fun argument to be had about informed consent.
It's fair to say that everyone know smoking is bad by now, but does everyone possess a correct and complete enough understanding of how and why to meaningfully consent to the risks? If you understand that smoking can cause cancer, but not that it can cause cancer even years after you stop smoking, is that good enough? If you think you can go on a cleanse and purge the toxins from your body, are you really competent to consent to the long-term risks? We don't let minors do nearly anything, from sex to signing contracts to receiving medical treatment, because we do not believe they are mature enough to properly weigh the consequences. If a minor decides to begin smoking, are they able to meaningfully consent to the risks, even if they have been adequately explained?
All medical interventions are weighing hopefully large benefits against hopefully small side effects, but even terrible side effects can be acceptable if the benefits are large enough and people receiving the treatments have been adequately informed and can meaningfully consent.
Well sure but I'm just pointing out that the analogy isn't great. There are already plenty of things minors can't legally do and we don't try to ban them for everyone.
It's not a question of illegal or not, it's a question of whether smokers are able consent to the risks of smoking, and therefore whether the companies are absolved of damages.
This is just an old woman being dishonest with herself. The US was the 1st to put warnings on tobacco packaging in 1966. This was about the time this woman started smoking. Is it really believable that an additional scientific data point about the harm would've swayed her decision? Especially one she wouldn't have even understood at the time? It's always been abundantly clear that inhaling smoke into your lungs is not a good idea - the scientific details aren't really necessary in making the decision not to smoke. What was necessary was a shift in the culture and advances in general healthcare which made the trade-offs worth the delayed gratification
There are plenty of people alive today who were unaware of the risks because until about the mid-80s the cigarette companies could actively deny them. You can only argue ignorance from when the mandatory product warnings were introduced.
I smoke (trying to quit) and I don't think cigarette manufacturers are doing anything immoral. I enjoy smoking! Why else would I have ever tried it when I knew all the risks?
Nobody is getting tricked, here. People are selling a product that other people want.
Have you read "the easy way to stop smoking"? He makes a great point about the claim that smokers don't actually enjoy it. It's addiction, thinking you enjoy it is a mechanism of avoiding the guilt of the addiction. Or something like that, his argument was much more convincing.
I doubt it, he would probably say no progress has been made at all:
"Many would still fell, as I did about five years ago, that a good prima facie case had been made for further investigation. None think that the matter is already settled. The further investigation seems, however, to have degenerated into the making of more confident exclamations, with the studied avoidance of the discussion of those alternative explanations of the facts which still await exclusion.
[...]
the B.B.C. gave me the opportunity of putting forward examples of the two classes of alternative theories which any statistical association, observed without the predictions of a definite experiment, allows—namely, (1) that the supposed effect is really the cause, or in this case that incipient cancer, or a pre-cancerous condition with chronic inflammation, is a factor in inducing the smoking of cigarettes, or (2) that cigarette smoking and lung cancer, though not mutually causative, are both influenced by a common cause, in this case the individual genotype."
https://www.york.ac.uk/depts/maths/histstat/fisher269.pdf
The current paper:
"Although we cannot exclude roles for covariate behaviors of smokers or differences in the biology of cancers arising in smokers compared with nonsmokers, smoking itself is most plausibly the cause of these differences."
http://dx.doi.org/10.1126/science.aag0299
Proof of smoking causing cancer was established a long time ago entirely without DNA evidence. I don't think convincing Fisher is/was important: there are several cases where he used his big brain to rationalize things that we clearly know are false.
>'Prof Stratton said in these organs smoking seemed to be accelerating a natural mutational process, but how it did this was "mysterious and complex".'
Wow, just wow. This is standard Armitage & Doll model that has been taught since the 1950s.
Every time a cell divides there is some chance of a genetic error occurring. The more generations away from the zygote a cell is, the more genetic errors it will have accumulated.
Activities that damage tissue, etc and necessitate cell division to replenish the cells will contain cells with more errors.
Now that is a vague sketch, but many people have implemented mathematical/computational models based on that idea, beginning with Armitage and Doll in 1954. Unless he is going to reject the model that has been driving cancer research for half a century (which should be noted in the interview), there really is no mystery at all.
OP's comment was succinct and digestible by a non-technical audience with basic biological knowledge. If he had known of the model, surely he could have spared 2-3 sentences like OP.
OP's comment misinterprets a quote; it's great to bring up that model, but it's ludicrous to think that Mike Stratton does not know it in far greater detail than nonbel, as I would place Stratton as the world's authority on cancer mutations. He was the senior author on the authoritative survey of cancer mutational processes:
In addition, nonbel's snarkiness and assumptions of ignorance end up misinforming HN readers more.
Scientists do not write these articles for the BBC. The reporters pick and choose what to take from the scientist, and report that. Most of the times they probably get most of the quote correct, or the scientist said something that had many of the words in the quote. But generally these types of articles are barely intelligible to the scientists that were interviewed for them.
Lets gather info from the paper and see if what they say makes sense. In discussing figure 1, they seem to know this data needs to be normalized to number of cell divisions:
>"The prevalence of somatic mutations was highly variable between
and within cancer classes, ranging from about 0.001 per megabase
(Mb) to more than 400 per Mb (Fig. 1). Certain childhood cancers
carried fewest mutations whereas cancers related to chronic mutagenic
exposures such as lung (tobacco smoking) and malignant melanoma
(exposure to ultraviolet light) exhibited the highest prevalence. This
variation in mutation prevalence is attributable to differences between
cancers in the duration of the cellular lineage between the fertilized egg
and the sequenced cancer cell and/or to differences in somatic mutation
rates during the whole or parts of that cellular lineage1."
And that they believe these mutations are accumulating at a relatively constant rate over time:
>"The mutations in a cancer genome may be acquired at any stage in
the cellular lineage from the fertilized egg to the sequenced cancer cell.
The correlation with age of diagnosis is consistent with the hypothesis
that a substantial proportion of signature 1A/B mutations in cancer
genomes have been acquired over the lifetime of the cancer patient, at
a relatively constant rate that is similar in different people, probably in
normal somatic tissue"
So now let's implement their model with the required assumptions:
Define the probability a mutation occurs during a given cell division as p.
Define the probability does not occur during a given cell division as q = 1-p.
Define the number of accumulated mutations required for carcinogenesis as n.
Define the number of cell divisions that have passed since the zygote as d.
Define the number of cell lineages in the tissue as Ncell.
Define the proportion of cancer cells that go on to form detectable tumors as C.
Assume the mutations can only occur once per cell.
Assume the mutations are occurring at the same rate (ie p1 = p2 = ... = pn).
The probability a mutation does not occur during division 1, or division 2, ... or division d would then be given by q^d (since p is constant we simply multiply the probabilities as for independent events).
The probability the mutation did occur at some point up to time d must then be given by 1-q^d. And for the n required mutations we would get
(1-q^d)^n.
We just derived the CDF of the geometric distribution, extended to allow for multiple parallel events. This is the cumulative probability of a cell lineage turning cancerous according to the mental model they describe in the paper, which is pretty much Armitage-Doll without mentioning the name.
To get the probability of a cell lineage turning cancerous at a given age (ie the pdf of this distribution) we calculate the first derivative of that function (warning: this is a continuous approximation of a discrete process):
-n*q^d*log(q)*(1 - q^d)^(n-1)
The expected number of cases per person after d divisions (division-specific incidence rate) would then be
C*Ncell*-n*q^d*log(q)*(1 - q^d)^(n-1)
You can see that only the height of the curve is affected by C and Ncell, the shape is independent of those factors. In the (non-simplified) Armitage-Doll model the shape of the curve depends only on the mutation rate and number of required mutations.
In that paper, they report seeing a range of roughly 10^-9 to 10^-4 cancer-specific mutations per bp in already detected tumors. If those arose after 10 divisions, the mutation rate would be 10^-10 to 10^-5 mutations/bp/division, etc. So we can see those values are empirically determined upper bounds on the mutation rates. So lets use the higher of the two as our value of p. Let us also assume only n = 2 mutations are need accumulate to result in a detectable tumor. Using R to make the upper plot:
p = 10^-4; q = 1-p; n = 2; d = 1:20000
plot(d, -n*q^d*log(q)*(1 - q^d)^(n-1), type = "l",
xlab = "Divisions since Zygote", ylab = "Pr(a Cell Lineage Will Turn Cancerous)")
abline(v = log(1/n, base = q))
Actually, by setting the second derivative of that CDF to zero, we can see that the Armitage-Doll model predicts a peak in age-specific incidence at log(1/n, base = q) divisions (vertical line on the upper plot). That 10^-4 value comes from Melanoma, so let us also look at the age-specific incidence for that cancer (lower plot). There we see the
peak incidence occurs at age ~age 90. So according to their model, the skin cells that are causing melanoma must be ~7k divisions separated from the zygote, corresponding to an average of ~78 divisions each year, or every ~5 days. Is that what happens?
Remember, we used a real upper, upper bound here on the mutation rate from their data, and only 2 required accumulated mutations. Even then we are getting into cells that are 78 generations separated from the zygote before being cancerous. What you will find is that the division rates required to fit what people really suggest (eg p=10^-7 and n=3) are insane according to the accepted model. If they have a different model than that, why do they not write it down and compare to epidemiological data?
This isn't like a long crackpot screed. It is a couple paragraphs... Why downvotes without explanation? Where did I go wrong (I see some typos at the bottom "78 generations separated" should be "7000", but that shouldn't be a huge deal)?
I didn't downvote, but it definitely does come across as a crackpot screed. You are discounting data in favor of an overly simplistic statistical model. You also greatly misinterpret a key point in the quote: they're not saying all mutations accumulate at a constant rate, but only a few signatures appear to. In fact, the very next sentence of that quote is:
>The absence of consistent correlation of all other signatures with age suggests that mutations associated with these have been generated at different rates in different people, possibly as a consequence of differing carcinogen exposures or after neoplastic change has been initiated.
This is a classic crackpot technique: selectively quote just the parts that you want them to say, twist it a bit further to your needs, then proceed with an overly simplistic, but supposedly impressive analysis. I don't know or really think that you are a crackpot, but the quoting behavior is quite telling.
Getting back to your original comment, you accuse the authors of this paper:
of not knowing what they're talking about. But in reality, you have already mistaken the type of process that's being talked about. Stratton is talking about a biological and chemical process. You're talking about a "random" process from statistics. An old theory, that uses simplifying assumptions that do not apply with this data.
And finally, the most obvious reason that the Armitage Doll process is not the best explanation is that AD were looking at the process of carcinogenesis. This paper is looking at the various processes of mutations that happen because of a carcinogen. These are different things, especially since mutational processes accelerate after carcinogenesis. I believe the paragraphs that you would find most interesting from the paper are here:
>Signature 5 is found in all cancer types, including those unrelated to tobacco smoking, and in most cancer samples. It is “clocklike” in that the number of mutations attributable to this signature correlates with age at the time of diagnosis in many cancer types (17). Signature 5, together with signature 1, is thought to contribute to mutation accumulation in most normal somatic cells and in the germline (17, 23). The mechanisms underlying signature 5 are not well understood, although an enrichment of signature 5 mutations was found in bladder cancers harboring inactivating mutations in ERCC2, which encodes a component of NER (24).
>Signature 5 (or a similar signature that is difficult to differentiate from signature 5 because of the relatively flat profiles of these signatures) was increased by a factor of 1.3 to 5.1 (q < 0.05; table S2) in smokers versus nonsmokers in all cancer types together and in lung squamous, lung adenocarcinoma, larynx, pharynx, oral cavity, esophageal squamous, bladder, liver, and kidney cancers. The association of smoking with signature 5 mutations across these nine cancer types therefore includes some for which the risks conferred by smoking are modest and for which normal progenitor cells are not directly exposed to cigarette smoke (Table 1). Given the clocklike nature of signature 5 (17), its presence in the human germline (23), its ubiquity in cancer types unrelated to tobacco smoking (18), and its widespread occurrence in nonsmokers, it seems unlikely that signature 5 mutations associated with tobacco smoking are direct consequences of misreplication of DNA damaged by tobacco carcinogens. It is more plausible that smoking affects the machinery generating signature 5 mutations (24). Presumably as a consequence of the effects of smoking, signature 5 mutations correlated with age at the time of diagnosis in nonsmokers (P = 0.001) but not in smokers (P = 0.59).
Armitage Doll relates at most tangentially to what is being reported by these scientists.
Thanks for responding, I hope to get back to you in more depth. But first of all:
>"An old theory, that uses simplifying assumptions that do not apply with this data."
Yes, get rid of one simplifying assumption that was originally introduced for computational reasons and is totally unnecessary today (low mutation rate), and you can see it is impossible for that theory fit the age-specific incidence data using accepted mutation rates + division rates.
Something is wrong, yet in the supplement of the Alexandrov et al (2016) paper, which has the same first and last authors as Alexandrov et al (2013) paper you cited, they use this model without comment on that issue.
Also, in the 2013 paper, Armitage-Doll is not mentioned but it is clear to anyone familiar with that model that it is guiding their interpretation of the results.
It really is not a complex concept. If that is too "mysterious and complex" of a process for the audience to understand then I doubt there is much point attempting rational communication with them. Note: I think the vast majority of people could easily understand my sketch above.
There is a difference between using statistical models and understanding the underlying processes. I can tell someone that when we smash together Muons and nucleons that there is a certain chance that we will produce Kaons. That, I believe, many can understand.
What I cannot explain briefly to a general audience is how quantum field theory and the standard model of particle physics works and how we can compute the probabilities from that.
Just because you know that something is happening, doesn't mean you understand anything about the underlying processes involved.
"when we smash together Muons and nucleons that there is a certain chance that we will produce Kaons."
I don't think that is a fair comparison. My description had much more content than this, it was a high level overview of the proposed process. In contrast, your example does not explain anything.
> Every time a cell divides there is some chance of a genetic error occurring.
> Activities that damage tissue, etc and necessitate cell division to replenish the cells will contain cells with more errors.
I don't see how your explanation could enable anything but a statistical model.
The underlying processes I'm talking about would be molecular interactions modeled through the domain of theoretical chemistry or even mechanical processes, probably involving the quantum mechanics of many particle systems. This is probably the mysterious and complex part that is not well understood. Your example does nothing to explain how that works.
Damage happens, yes, this much is clear, but how do the molecules of smoke interact with the cells in the lungs and other places in order to cause the mutations? Can we compute what happens when a nicotine molecule hits a lung cell? Probably not... because it is too complex and mysterious.
"I don't see how your explanation could enable anything but a statistical model."
First, I wouldn't call Armitage and Doll a "statistical model", it is more a "rational model" derived from first principle considerations. "Statistical models" are stuff like linear regressions, at least to me.
Second, my explanation is useful in that if it is correct, we would need a certain combination of division and error rates to explain age-specific incidence curves. So, within the context of the model (which is commonly accepted), we can put upper lower bounds on these values from epidemiological data.
See for example my earlier discussion on this site[1]. Even if you disagree with my conclusions (somatic mutation can't do it... something is up and hundreds of billions to trillions of $ have been wasted barking up the somatic mutation tree), or find a mistake, that is still what it can be used for:
First, from Wikipedia [1]: "The Armitage–Doll model is a statistical model of carcinogenesis [...]"
Second, the paper itself [2] talks about cancer rates and uses experimental data for it (I just glossed over it, so I can't give a decent summary). This is a statistical model.
I think we disagree since you misunderstand what the term statistical model means. Furthermore, you are misusing the term "first principles." First principles really means that you start from a well established theory that describes how something works. From there you predict mathematically, or with a computer simulation, what the reality is. Using experimental data is strictly forbidden.
From Wikipedia [3]: "In physics and other sciences, theoretical work is said to be from first principles, or ab initio, if it starts directly at the level of established science and does not make assumptions such as empirical model and fitting parameters."
I generally have no idea about cancer research, so I have to trust you and cannot comment on the usefulness of the approach.
1) The original implementation of the Armitage-Doll model contains simplifications made for computational reasons that mess it up. You can easily see this by checking that the probability of a mutation per cell goes over one (see eq 1 in the appendix of Armitage and Doll 1954). Check the link to my earlier discussion on this site for the corrected version. BTW, I also see some discussion of Armitage & Doll in the appendix of the current Alexandrov et al. (2016) paper (they use the simplified version of the model).
2) Every model is originally based on some kind of observation. The Armitage-Doll model is basically "cancer is caused by the accumulation of errors in a single cell", then they go on and do the math from there. Sure, it would be great to know exactly what those errors are, how many it takes, which cells, etc so that we can constrain all the parameters. You are saying that "from first principles" precludes having any parameters, either free or determined by data?
3) As I said, I think the above is quite different from a statistical model like y = a +b*x + eps. Note: In some cases you can deduce an equation like that from an idea like Armitage-Doll, which is fine. Armitage-Doll definitely has more content to it.
>"The original implementation of the Armitage-Doll model contains simplifications made for computational reasons"
Quoting myself rather than editing...Actually, I forgot they come right out and say it:
"This result will be valid for large values of t (of the order of
a human lifetime) provided that p1t, p2t, y, prt are all sufficiently
small (as could be assumed in an application of this theory to
human cancer)."
http://www.nature.com/bjc/journal/v91/n12/pdf/6602297a.pdf
But with low probability of mutation at a given site p, how can you get their model to turnover (as is seen in the age specific incidence data)? I don't think you can, however the turnovers easily appear if you allow high mutation rates along with high clearance rates. But those high mutation rates are inconsistent with the estimated mutation rates in human cells.
Anyway, I hope someone checks into it because something is wrong with the mainstream model of carcinogenesis.
Edit:
It is also possible the data used to give the age-specific incidence (ie SEER) is fatally flawed and those turnovers are artefacts.
The first line of Wikipedia's entry states "The Armitage–Doll model is a statistical model of carcinogenesis, proposed in 1954 by Peter Armitage and Richard Doll, which suggested that a sequence of multiple distinct genetic events preceded the onset of cancer."
It's clearly a mathematical/statistical model of a phenomenon and not an explanation of the underlying processes.
There are lots of DNA repair mechanisms, as well as checkpoint mechanisms that prevent damaged cells from dividing further.
However, as with anything digital, there is some error rate still. The most common type of cancer mutation will deactivate, p53, a protein that is one of the checkpoint genes.
Having an error rate is essential for evolution and variety, so its not entirely a bad thing.
Unless I am misunderstanding something, their figure 3 seems to be plotting effect size vs p-value... So all it would be showing is that they had more data from lung adenocarcinomas (ie sample size is larger for that cancer type). It isn't 100% clear to me if they shared the data used for that figure, but here are the frequencies each cancer type appeared in table S1:
Acute myeloid leukaemia (AML) Bladder
202 399
Cervix Colorectal cancer
168 559
Esophageal Adenocarcinoma Esophageal Squamous
242 292
Gastric cancer Kidney
472 257
Larynx Liver
123 392
Lung Adeno Lung Squamous
678 175
Oral cavity Ovarian cancer
363 458
Pancreas Pharynx
239 76
Small Cell Lung Cancer
148
"Comparison of overall methylation between smokers and non-smokers was performed for all tobacco-associated cancer types for which there were available data from Illumina Infinium HumanMethylation450 BeadChip array, where each array contains 473,864 autosomal CpG probes. The examined data were downloaded from the original data source (Table S1)
[...]
distributions were subsequently compared between smokers and non-smokers using a two-sample Student’s t-test. Results were considered significant for Bonferroni threshold of 10-7."
So it is not like figure one from that Lew paper, because their effect size is not normalized to the inter-individual variance. This is a point in their favor.
However, the sample sizes do match up to those found in table S1 (which I posted above). From the data provided, we cannot tell whether that difference in p-values is solely due to sample size or not. They need to tell us the variance for each CpG/tissue combo as well.
"In the absence of mutagens, an average gene will mutate about once in a million generations. ~10^16 cell divisions occur in a typical life span so somewhere in cells that are part of you each of your genes has mutated 10^10 times (hence cancer). Only mutations in the germ line can be passed on to the next generation. You have about 50 mutations that your parents dont have (mutations that happened in the egg or sperm that made you up)-each of your parents in turn have passed on ~50 mutants that their parents dont have."
Source: an email from my undergrad genetics professor
I read the original study and yes, they did compare it to lifelong non-smokers. However, as far as I saw they only compared people with cancer. And the numbers were usually increased for smokers and the smokers usually ended up with more of a certain kind of cancer.
I wonder if there is just about anything (other than water) that you can put in your body that wouldn't have some effect on the mutation rate of some particular cells in your body.
Of course, that seems to be exactly what is going on:
>"These considerations of mechanism suggest that at chronic doses close to the toxic dose, any chemical, whether synthetic or natural, and whether genotoxic or nongenotoxic, is a likely rodent and human carcinogen. Not all chemicals would be expected to be carcinogens at high doses; the MTD may not be reached (101) or the chemical may be toxic without causing cell killing or mitogenesis."
I wonder if that's due to the other stuff typically added to chewing tobacco.
It'd be interesting if tobacco could be safer, but isn't, because the manufacturers don't want to incur the expense and anti-tobacco folks want to keep people from smoking at all, not make it safer (c.f. vaping, which is — I think — basically harmless and yet is banned as much as smoking is).
> The most harmful cancer-causing substances in smokeless tobacco are tobacco-specific nitrosamines.
> Cancers linked to the use of smokeless tobacco include:
* Mouth, tongue, cheek, and gum cancer
* Cancer in the esophagus
* Pancreatic cancer
You can also get other kinds of mouth and tooth problems, and of course nicotine is still a definite health risk.
If there were a way to make tobacco healthy, I think the manufacturers would have spared no expense to do so, because the death of a customer prevents them from spending more money on what is sold.
It's based on roasting/burning it, the same reason why meat is cancer-causing. That's also why Swedish snus probably isn't cancer causing, because instead of being roasted, the tobacco is steam pasteurized.
I can't imagine that cigarettes would work with steamed leaves.
edit: And you'd have to vape the steamed leaf cigarettes, of course.
You get DNA damage from a lot of different sources, from food to viruses to radiation to industrial chemicals to just plain replication errors.
I agree vegans probably still get cell damage from the food they eat, but that's not proof positive because they would still die from cancer even if they didn't.
Alcohol can cause inflammation, triggering various parts of the immune system to kick in. This could result in the release of free radicals from these immune cells, which promotes DNA mutations.
And surprisingly no mass deaths from cancer of Russians or Irish were detected, with both nations famous for alcohol abuse. Yes, alcohol is harmful, but like Russians joke, it only kills weak brain cells.
Maybe a lot of people die before they get cancer from it? Like organ failure (liver, kidney, heart) way before they develop cancer (symptoms)? Or get into accidents (car, freezing to death) etc. It is like people saying smoking can prevent Alzheimer as statistically people who smoke a lot have less instances of it. Because they die from that habit before the Alzheimer shows up.
OTOH moderate intake of alcohol, despite the risks, also has positive effects on the cardiovascular system. Wine has antioxidants which are associated with longevity, beer is good for bone strength, and so on. While an alcoholic may have a higher chance of dying before cancer gets them due to organ failure and accidents, a glass-of-wine-a-day drinker might live longer with a higher quality of life with the increased cancer risks than they otherwise might have with their congenital heart disease or whatever. Cancer typically gets you when you're old, heart disease gets a lot of people in their 40s and 50s.
And while the first world doesn't benefit directly anymore, typical brewing and fermenting processes ensured a drink was sanitary due to lengthy boiling times or yeast out-competing other microbes. Alcohol and hops/flavorings provide antimicrobial effects, acetobacter competed and inhibited against other water-born bacterial and mold growth. Alcoholic beverages are an easy way to store and preserve calories in times of scarcity, etc. It's quite likely that those who chose low-alcohol beverages were saved from other water-born diseases and lived longer thanks to it.
Well, if they die close to their 90-ies, and with no cancer, its a decent lifespan. This is what I learned from my granddad, who was great chess player, famous school teacher, and volcanic smoker.
At least here in the EU and especially this year for some reason, a lot of news has been doing the rounds that push research like [0] to the public. My parents doctor, since only a few months, now calls alcohol dangerous poison and something you should never use, like smoking. Although it's not new research, it seems more people are listening recently.
It causes swelling which cause more blood to be in that area which make the organs hotter. But I really doubt you could get any real burns from an inflammation.
So how much more is it compared to a non-smoker? I understand the idea of shock factor but everyone gets mutations, it would be nice to get a baseline.
Evolution doesn't have a high or low state, or a linear progression. It's a natural process that is random and responsive to environment changes, not progressing towards an ideal.
If mutation is the engine of evolution, an increase in mutation should mean an increase in the speed of evolution. Obviously not on the scales we're talking about here, but the premise doesn't seem too unsound, external pressures being equal.
The premise is highly unsound. This study is talking about somatic mutations, which can only be harmful to an organism. Why? Because they can be beneficial to an individual selfish somatic cell, which is what we can cancer. In other words, when a somatic mutation is succesful, it spreads and becomes cancer. And of it doesn't spread, it can't have a serious impact on the phenotype of an entire organism.
So, the mutations discussed in the article have nothing to do with evolution, because they are somatic, and not passed on to offsprig. But even if smoking caused germ cell line mutations, it's also important to note that "highly evolved" is a mostly nonsensical phrase that has no real meaning, and there is absolutely no guarantee that any individual germ line mutations would confer a selective advantage to the off-spring- in fact, the majority of the time, specific mutations are neutral or harmful. Thus, even if smoking did increase the mutation rate in the germ line of a smoker, any given smoker kid would probably just have more problems than benefits. And because mutation rate is (maybe this is somewhat controversial) a phenotype that can and has evolved into itself, changing it artificially through smoking would likely result in a net reduction in "evolvability" as it has been called. Anyways these are all long term (and I mean LONG) population level effects and have nothing to do with individuals being "more evolved".
Just trying to make the point that the original assumption was three times removed from a sound understanding of evolution and showed some pretty big misconceptions.
"Can only be harmful" is pretty strong. You could have a set of mutations in a T-Cell for example that makes it super good at killing all forms of cancer.
You could get a 'super T cell' that behaves just as you want, or as is empirically observed, mutations would more commonly lead to leukemia.
There is a phenomenon call somatic hypermuatation, that as T-cell respond to antigens, they 'get sloppy' in coding their DNA to optimize the response. It' has also been linked to blood cancers, so it is a risky approach, like many aspects of immunity.
Of course almost all mutations won't be beneficial (this is also true of germline mutations). But "can only be harmful" seems to imply that beneficial mutations are impossible.
agreed. sort of my point: some changes can be beneficial, but the process is very risky and the cell goes through great measures to minimize any sequence changes. some viruses are sloppy on purpose, as they have tens or hundreds of thousands of offspring, so trial and error is acceptable.
I'm still skeptical- I doubt a single T-cell can have anything but a ever so slight statistical inpact on the phenotype of an entire organism, and there is no selective process to keep that mutation around, so it cannot last long in the body, either.
That's definitely not obvious. I would agree that mutations due to smoking could be in majority harmful due to the chemical components and the high temperatures involved. Other than that, a mutation is a mutation, whether due to smoke, nuclear irradiation, high altitude, or chance. In all cases, they can be beneficial or harmful. The evolution process will then cause only the beneficial ones to perdure.
> The evolution process will then cause only the beneficial ones to perdure.
This isn't correct and is a common misconception about evolution. The process which does this is natural selection, and it only occurs through the organism being unable to reproduce as well as an organism with beneficial evolutionary changes.
With humans in the modern world, there is no natural selection because of state benefits that keep people alive and able to reproduce who would usually be unable to do so in a world without safety nets.
So in the modern world, any evolution in humanity - either positive or negative - will perdure. In effect we've ended the traditional form of evolution ages ago when we became civilized.
Another common misconception is that evolution can only occur via natural selection. Assortative mating[1] can still drive evolution for segments of the population, if not necessarily the whole population.
Also, the entire world does not have modern safety nets, not even close.
In USA, families on welfare benefits are also often the largest families. Being laid more is irrelevant if it does not result in a child. It's more reason as to why evolution is simply not a factor in the modern world.
Also, why do you say 'some'? It would stop all negative mutations, as all people are given the ability to reproduce. Your argument seems to be that people with negative mutations would not be attractive, but often they are attractive to others with negative mutations themselves. Or just people who no longer breed purely based on biological fitness - again because of modern civilization.
You have already said some people have larger families than others and these people have differences than others thus contradicting your premise where there is no longer evolution in human genes.
I never said there is no evolution? I said there is no longer a link between positive and negative traits and the ability of someone to reproduce. Whether someone has positive or negative mutations is no longer a factor in their survival, and so there is no natural selection of positive traits.
There is definitely no contradiction there. Genes will still evolve, but it will no longer be through a process of natural finding the most positive genes. Or I'd guess you could say that we will now evolve towards genes that enable the largest families. And the largest families are predominantly in poor suburbs. The actual environment is artificial though, as those families would not be able to survive on their own without support. Taken to an extreme, it would technically be 'evolution to destruction' by selecting for negative traits that make it impossible to survive outside of the safety net. Luckily we're nowhere near that kind of extreme.
> positive and negative traits and the ability of someone to reproduce.
What's "positive"?
> The actual environment is artificial though, as those families would not be able to survive on their own without support.
I apologise to those who are offended by my stereotyping - If anything, I'd expect it's some of these people who are most able to survive on their own in the scenario of nuclear apocalypse and all major cities destroyed.
In such a scenario people like software engineers on HN, may even have lack the traits for survival (inherited or learned) - many of us do not know how to fix our own cars or grow our own crops.
It's funny how only one of those things you listed is a voluntary activity.
Anyway, by all means, continue smoking if you think it's going to give you some sort of superpowers or immunity that you can pass on to your progeny. Most likely it'll just give you a disease.
I suspect there are multiple reasons for the DNA changes. One that comes to mind is the number of times the lungs have to repair themselves due to the tar and other contaminants. The hot smoke might even contribute to the tissue damage. Cancer is uncontrollable cell growth. The cell/body's ability to control a certain type of cell division has been lost.
So, my thinking is, in the same way that you lose quality as you make a copy of a copy in a copy machine the same happens to the cell's DNA. The more a cell has to divide the less the DNA can remain without errors. DNA can tolerate a number of errors but it can eventually lead to cancer. My guess is that not one issues causes the DNA changes but and array of them given the number of substances a cigarette has.
I wonder if there were studies that analyzed the effect of smoking non-industrialized cigarettes. I smoke 2-4 cigarettes per day and make my own cigarettes from tobacco leaves that I dry/shred myself. The leaves in turn come from a few organically grown plants.
The quality of tobacco does not matter. Homegrown can be even more harmful.
The main reason tobacco is so dangerous is because you are inhaling smoke and carcinogens that are created in the burning. Burning organic or non-organic makes no difference. You are like firefighter in a burning house without a mask when you inhale.
People vary in what gives them pleasure and in their valuation of the time/pleasure trade-off. Cigarettes are a tool for some people to move pleasure from the future to the present (i.e., shorter life/less future pleasure in exchange for more pleasure now); they adress intertemporal pleasure-flow needs for some, much as loans address intertemporal cashflow.
Because people like to smoke. It's more than pleasurable, but only iff you are able to either ignore or accept the consequences (or you are simply not aware of them).
I guess the difficulty with this is that we're faced with groups that are actively telling us what to do by ways of advertising. They ask more nicely, and are at times much less obvious, but it's still has a great influence.
I'm perfectly fine with cigarette advertising being illegal, mandatory blank packages, and so on. I'd be very angry if they completely banned cigarettes, though.
Me too. I'm just weary of it appealing via marketing to those without the skills to fully understand their choices or to understand that their are being advertised to, like children.
Then move to North Korea, I already wrote this before.
If you want to live here you either accept that you are in a society of free people who actually have a free will or you move somewhere else where you'll find like minded drones serving their dear leader who in turn takes care of them like a father figure.
We are not going to give up our freedom and turn into weak minded persons just to accommodate you.
I'm not even in your country, and honestly, I don't want to live there. Where you see people shouting "freedom" the loudest, I see fear, distrust, and anger. I'm just pointing out that no one is as free as you think you are because you always have influences. But I appreciate your willingness for open thought and reflection.
You just "point it out" to convince me to casually accept regulating other peoples or other companies freedom to advertise away because you suppose that people are just sheep who can't help being controlled by it.
On top of that you probably do not even realise that you are arguing here for limiting freedom of speech.
> Where you see people shouting "freedom" the loudest, I see fear, distrust, and anger.
Am I supposed to feel bad now? I don't, I still want to keep freedom of speech.
> I'm just pointing out that no one is as free as you think you are because you always have influences.
Ominous and sometimes invisible influencers everywhere. Best way to deal with it: Censorship.
Sorry, I don't believe in absolute freedom of speech. In fact I don't believe in anything absolute. But enjoy your black and white world. It appears to be a very angry place where one either lives in a fictional idealized America or North Korea.
Well, here's how I see it. I understand what you are trying to say, it is not your (or anyone's) business to decide what other people should do with their lives, specially if it doesn't affect others. And, so no one (or governments) should intervene and regulate/ban sale of cigarettes. Would you feel absolutely the same way about all banned substances? If not, well you should agree that different people would draw the line differently.
> Would you feel absolutely the same way about all banned substances?
Yes, absolutely. If people want to ruin their lives it's not my responsibility to keep them from doing it. It's their own decision and all consequences are their own problem.
This is an absolutist view, while it is quite a compelling argument for certain extreme cases, I am afraid the world is never that black and white. Since we are talking about regulating/banning substances, let me try to point it out with a relevant example. While it might seem fair to say that if someone wants to ruin their own life by substance abuse, why should it be my (or the government's) responsibility to keep them from doing it. But, consider this, one of the growing problems right now in the US is opioid dependence and addiction. In these cases, these opioids are medication that is prescribed by doctors to treat acute pain. But, along with providing pain relief, this medication can cause opioid dependence and addiction over time. A sizable population of regular people who were just seeking treatment for their illness, unfortunately ended up with opioid addiction. This could just as easily happen to any of us or our loved ones. I can't speak for you but I would definitely want the government to step in, fund relevant research to study the problem, based on that perhaps regulate (or ban, if necessary) the availability and/or prescription of such medication because though it provides pain relief, it has unintended consequences that ruin lives of unsuspecting people.
Government regulation isn't necessarily always bad. There is no absolutist one-size-fits-all solution for all problems. Would I like the government to tell me what I can and cannot do, absolutely not. I would protest with you if I think government is overreaching. But, would I concede that there are certain issues (which might not affect me, but might affect lot of others) where the government has to intervene, of course, yes.
I guess the last few years of news contradicting that fat is bad for you, salt is bad for you and so on had made me believe the legend was long ago punctured.
I would look into Ancel Keys and the diet heart hypothesis.
This idea isn't, and never was grounded in evidence. It's based on very poor science done in the 20th century. The old guard of doctors and health officials will be looked at in the same way we look at geocentrists now. They hold a lot of the blame for the current obesity crisis we have.
while there are some studies that do not put marijuana smoking as high on the danger list [1] I am really curious that as legalization increases what will we see in the future. Then of course there is the loosely regulated area of vaping and who knows what is in some of those fluids. For the most part I am quite sure they have to be safer than smoking but I would love some hard regulation.
I think it ultimately comes down to the vaporization tool. Older brands and vaporization techniques used by things like the Volcano or Silver Surfer, I would consider pretty safe. But once you get into the lower budget vaporizers, e-cigs, wax on metal coils, I think it gets more sketchy and its harder for the consumer to determine quality
As a pipe smoker, I can tell that vaporisers work with synthetic liquids containing synthetical nicotine, nothing to do with harms and benefits of tobacco. You could use nicotine plasters with the same effect.
Is there anything you can do to help your odds of not dying from lung cancer once you have stopped smoking?
Any yearly tests to perform?
I was a 10cigs a day smoker for 15 years(quit some years ago) and it really weights heavy on my mind that there is nothing I can do about my past mistakes.
I've once read somewhere that they polled heroin addicts, asking them what they'd rather do first time they wake up in the morning - shoot heroin or smoke a cigarette.
Of course the vast majority said they'd smoke a cigarette.
I've never been a heroin addict, but I've been a tobacco smoker for many years and I can confirm that smoking a cig was definitely the most important thing I had to do in the morning.
Also if I had to spend my last money on food or a pack of cigarettes, obviously and without further consideration, I would choose the cigarettes.
I'll just note that these patterns aren't universal. I have been a smoker for almost 20 years (with some prolonged breaks along the way (one lasting around 3-4 years)). I almost never smoke in the morning (and never did). I currently smoke no more than a pack a week, easily skipping several days at a time.
I started with Lucky Strike, then smoked Marlboro Lights for about 18 years, then the last two years or so I smoked organic rolling tobacco - Cross Road.
I've stopped smoking 18 months ago, but even after 1.5 years, I still get the urge to smoke almost every day.
I've stopped smoking a week ago and brain fog is killing me, I'm not able to do my job any more, any advice ? I just sit and stare at monitor without my brain working :/
Yes. This will go away after a couple of weeks.
Depression is a common side effect of quitting, so hang in there.
First 2 weeks are the hardest, then it slowly gets easier.
There are few short term advantages to quitting smoking - your sense of smell improves and you have more spare time on your hands - other than that, there's little to brag about.
By going through this short term suffering, you're improving your long term health.
If someone (God) came to you and said: "Hey, I'll add 10 healthy years to your life if you agree to go through a period of feeling shitty and some mental fog and restlessness and nervousness for a couple of months".
I guess we'd all agree to such a deal and it's pretty much the deal you have right now, so hang on.
> The danger is in the smoking, not the addictive substance.
Actually, that's incorrect. Nicotine acts as a stimulant and constricts blood vessels, which causes all kinds of serious circulatory problems in the long term - high blood pressure, heart attacks, strokes and so on.
Unfortunately there's no easy way around nicotine, you just have to stop ingesting it.
The gum/patch can alleviate the withdrawal symptoms, but you'll still have to quit the gum.
A 2013 Gallup Poll finds that 92% of successful ex-smokers did not use the nicotine patch, gum, Zyban, Chantix or Champix, that most quit smoking cold turkey.
"There are some studies of prolonged nicotine replacement therapies (NRT) in smokers who have quit smoking. In these studies, no adverse effects have been found when nicotine medication was administered for months to several years. Other studies indicate that patients with known cardiovascular disease tolerate NRT well for periods up to 12 weeks. "
By far, the danger is in the smoking, not the nicotine in your bloodstream.
allowed an open-ended response, so someone "might have decided to quit" or quit because "it was time" but also used an NRT to help them through the cravings and not have mentioned that to the interviewer.
My own experience confirms this. I am not addicted, I started well after thirty and I only smoke real tobacco. Instead of mental fog on a month without tobacco I am getting the previous default state of mind, and after a pipe, I am getting very cool focus.
Cigarettes except your last one roll it yourself real tobacco contained additives that made you neural system very succeptible to nicotine, there is biochemical evidence for your case. Were you using plasters like Nicotinelle to quit, or just took off on a bare will?
"Animal studies by NIDA-funded researchers have shown that acetaldehyde, another chemical found in tobacco smoke, dramatically increases the reinforcing properties of nicotine and may also contribute to tobacco addiction. The investigators further report that this effect is age-related: adolescent animals display far more sensitivity to this reinforcing effect, which suggests that the brains of adolescents may be more vulnerable to tobacco addiction."
I'd be interested to know how variable it is from person to person. I had long-term (>1y) treatment with reasonably high doses of fairly mild opiates (tramadol/codeine) twice, as well long-term treatment with benzodiazepines, and each time I literally just stopped - no tapering or dose reduction, no withdrawal or ill effects (aside from the original pain returning), and no cravings to seek more
Cigarettes, on the other hand, I've smoked a couple of times (1 or 2 cigarettes each time), and every time there's been this thought at the back of my head "I should get some cigarettes" for most of the following day. It's obviously not addiction and easy enough to ignore, but it's definitely a noticeable effect. Interestingly two lengthy (4 hour plus) shisha sessions didn't have the same effect (was a little light-headed and felt like I'd had about 50 cups of coffee, but no effects or cravings the following day).
Actually I believe clinically, "addictiveness" is measured by what it takes to develop a dependence in the first place, rather that what it takes to get rid of that dependence or even the physical effects of an abrupt cessation. I heard somewhere (sorry no references) that by that measure, nicotine is one of if not the most addictive substance known.
I think your definitions are almost correct here. Addiction is actually defined as a medical condition ”characterized by compulsive engagement in rewarding stimuli despite adverse consequences". So addiction is technically a mental thing and susceptibility to it depends not just on the drug, but on the person, mentality, self control, etc. When a lot of people talk about addiction they are actually thinking of dependence, susceptibility to which is only dependent on the drug and the amount of use. You can have one, or the other, or both.
I believe that while both nicotine and opiates can be addictive from first use, it takes a much longer prolonged use of nicotine to form a strong physical dependence (from personal experience, on the order of a few years of regular use), unlike opiates which can form a strong physical dependence after just a short time (as little as just a few weeks of regular use).
I think you need very large quantities of whatever is in tobacco that makes you addicted to have physical dependency on it. (Is it nicotine?)
I smoke a pipe on weekends. I have no physical craving for tobacco during the week and sometimes I just don't want to even on the weekends. The most amount of cigarettes I had throughout my life was probably equal to one pack and I never inhaled it because I don't feel like choking on smoke.
The worst effect I get with nicotine is dizziness but never any physical dependency or withdrawal from its absence in my body.
I just wish they did more studies on the effects of occasional use of tobacco, via pipes and cigars to see the effect of what occasional smoking does to someone.
I love nicotine despite the "factoid" about its' addictiveness I listed above, and I say that as a former smoker (sometimes up to a pack a day, for about 6 years). I'm actually at the point where I can smoke occssionally and not feel the need to keep smoking, although I would simply prefer to vape anyway, personally. I too would like to know more about the effect of occasional smoking.
So, could we detect what properties of smoking map to which DNA changes, and design a cigarette that maximizes net-positive DNA changes while minimizing harmful/negative ones?
Not much literature on vaping as yet. However, British authorities currently consider vaping to be significantly safer than smoking, and encourage smokers to switch in order to help them quit.
Also, vaping fluids don't contain the many, many compounds which are present in tobacco smoke and known to be dangerous, so it seems quite likely it's significantly safer. The unanswered questions are over what long-term inhalation of vaping fluid might do.
A significant amount of the shredded brown innards of most modern cigarettes is a paper product called "reconstituted tobacco" or "homogenized sheet tobacco," which is made from a pulp of mashed tobacco stems and other parts of the tobacco leaf that would otherwise go to waste. Manufacturers spray and impregnate reconstituted tobacco paper with nicotine and other substances lost during the process, along with as many as 600 chemical additives. These include several that may come as a surprise, such as ammonia, which aids in the delivery of nicotine, and chocolate, which masks the bitter taste of tobacco. Finally, the 'recon' is sliced to resemble shredded leaf tobacco.
So basically good research should compare people smoking quality cuban (once a week) with pipe smoker (once a day) with this poor creature addicted to synthetical 'tobacco' on her 20/day. And of course, since urban people are exposed to contaminated air from cars, control group must be taken from rural areas. I predict result that tobacco is not responsible for lung cancer, in absence of other air contamination factors.
You know, more than 90% of people with lung cancer ate cucumbers. So think twice before blaming tobacco.
I've heard this argument before. The claim that "clean" tobacco smoke is not carcinogenic and only the additives are to blame. Well, hate to burst your bubble, but when you burn tobacco--additives or not--you are creating hydrocarbons like benzene, bezopyrene, and butane. All of which are carcinogenic and will cause mutation in human cells upon contact.
You cannot remove these hydrocarbons from tobacco as they are only present during pyrolysis.
That book is authored by Alan Rodgman (bio below).
After joining R.J. Reynolds Tobacco Co.’s research department in 1954, Rodgman initiated the company’s research on cigarette smoke composition. He personally conducted and actively directed environmental tobacco smoke research until 1987.
Rodgman became director of research in 1976. During his career, he served on the editorial board of Tobacco Science, the Council for Tobacco Research, the Coresta Scientific Commission and several U.S. government tobacco-related committees.
He was a member of the Chemical Institute of Canada and the American Chemical Society for 60 years and a member of the New York Academy of Sciences for 40 years.
Rodgman published numerous scientific papers on tobacco smoke composition and served as a reviewer for tobacco-related manuscripts. In 2003 he was awarded the inaugural Tobacco Science Research Conference Lifetime Achievement Award for his tobacco-related research and activities. In late 2008 Rodgman co-authored The chemical components of tobacco and tobacco smoke, for which the authors jointly received the 2010 Coresta Award.
Of course, that's all also true of woodsmoke, and while some (IMNSHO, deluded) people are trying to ban fires, charcoal cooking &c., the societal consensus right now is that it's okay.
As a smoker I have special interest. There is no archaeological evidence of cancer among aboriginal nations of Americas which cultures had a lasting tradition of smoking tobacco. Cancer became plague with development of industry, and proliferation of lazy lifestyle.
"As a smoker I have special interest. There is no archaeological evidence of cancer among aboriginal nations of Americas which cultures had a lasting tradition of smoking tobacco."
Well, as a past smoker I too have special interest. But also, as a logical person, I'd expect all you'd find of cancer in "archaeological evidence" of human remains are those which afflict bones. So you're not really making a case. Also:
smokers get cancer, tobacco contains carcinogens, however, studies rarely take enough account of the wide range of conditions that contribute to health, stress, nutrition, socio-environmental conditions, mental health, exercise, meditation and mindfulness, these are often left out, clearly they have an effect, it's not an easy task, I'm not an advocate of ingesting harmful substances, I am an advocate of interdisciplinary research that helps us understand the why and how humans are susceptible to what seems like 'wrong choices', or are they, see 'The Paris Problem', problem eh... don't forget the man in the dark street searching for his lost keys only under the light from a streetlamp..
No problem, mate, its a free country. I mean Russia, of course. In the US there are established opinions that firms censorship which you just exercised.
* did you even read what you linked ? it is arguing semantics:
>If they would say that smoking increases the incidence of
>lung cancer or that smoking is a risk factor in the
>development of lung cancer, then I would agree. The
>purpose of this article is to emphasize the need to use
>language appropriately in both the medical and scientific
>literature (the media, as a whole, may be a lost cause).
What the author was smoking? 20 a day of what? Cigarettes? These things have nothing to do with tobacco. Cigarettes are purely synthetical things. The real research could compare say, avid snus user with cigars smoker with pipe smoker with cigarettes smoker with marijuana smoker, with non smoker exposed to industrial work, with non-smoker exposed to work in civil construction, and so on. Poor isolation of factors and lack of statistics are signs of fake research.
Polonium-210 in tobacco contributes to many of the cases of lung cancer worldwide. Most of this polonium is derived from lead-210 deposited on tobacco leaves from the atmosphere; the lead-210 is a product of radon-222 gas, much of which appears to originate from the decay of radium-226 from fertilizers applied to the tobacco soils.
https://en.wikipedia.org/wiki/Polonium#Tobacco