On the importance of luck [Pharyngula]


That paper that proposed that most cancers were due to bad luck, that is, that they were a consequence of biological factors that could not be controlled, has been surprisingly controversial. I thought it was a fairly unsurprising paper that confirmed what we already suspected, but wow, the furious pushback has been something to behold.


Today, though, a couple of MDs have responded to the paper and reinforce what I said.



Steven Novella thinks the general logic is sound.



This is an interesting study and it will be interesting to look at replications and other methods, if they are available, of making the same sort of estimation. What this study suggests is that at least 2/3 of all all cancers are due to random mutations – bad luck. The figure may be higher once breast and prostate cancers are included. Of the remaining third it is not clear how much is due to inherited genes vs lifestyle factors.


The logic of the study is sound, in my opinion. The authors assume that lifestyle and genetic factors affect the risk of tissue specific cancers, but not cancer in general. This study would miss, however, lifestyle or genetic factors that affected the risk of all cancers (regardless of tissue type) equally. One might argue, therefore, that it overestimates the role of random mutations, but that is only if you accept that there are universal risk factors out there.



David Gorski emphasizes that the result actually fits well with prior estimates of the relative contribution of environmental/genetic factors and a probabilistic component.



That cancer is due to a combination of random probabilistic processes, environmental exposures, and heredity is a non-controversial statement. What is controversial are estimates of the relative contribution of environment, given that the percentage of cancers due to inherited cancer-causing mutations is known and low. Take the example of breast cancer, which is a cancer for which environmental and lifestyle contributions are not particularly high, with perhaps 27% of breast cancers being due primarily to environment (which includes diet and exercise, as well as hormone replacement therapy). The vast majority of those environmental contributions come from obesity and alcohol consumption, neither of which reaches the double digits, percentage-wise. Yet there are organizations that promote the idea that “chemicals” in our environment are a major cause of breast cancer. Unfortunately, about 5-10% of breast cancer is inherited, while perhaps up to 27% has a strong environmental component. That leaves around 60% of breast cancer (or, even using higher estimates, at least 50%) as falling into the “we don’t know” or “stochastic” category, with, sadly, nothing that we know of right now that can be done to prevent these cases, while the 10% of hereditary cases can only be prevented by aggressive means, such as chemoprevention or prophylactic surgery.



I still find it interesting, though, that so many people have complained to me about ascribing phenomena to chance — there are some serious misconceptions floating about out there, and I’ve always taken these ideas for granted. I guess I can’t. David Colquhoun and I spent an enlightening afternoon yesterday trying to get through to a few people on Twitter who could not believe we actually thought chance was a reasonable explanation for anything. I did not have the impression that these were anti-science people, or creationists, or anything absurd like that — they just had a striking psychological antipathy to the whole idea of random effects.





no not chance. There must be factors of which we are unaware. U can’t abandon sci. method!






Luck, by definition, has no cause therefore unscientific.






random does not mean without a cause – which is what luck means :-)



Fascinating. Random events are not even scientific? Where did this idea come from? Everything has to have a “cause” of some sort? Weird.


Maybe it’s because a lot of my early training in biology was in genetics, and there you acquire a strong appreciation for the importance of chance events. Genetic gene mapping, for instance, is done by looking at recombination frequencies — the probability that a meiotic crossover event will occur between two genes on the same chromosome, which is a factor of the physical distance separating them. We understand the physical basis of this event, which involves a protein, Spo11, that binds to a random location on the chromosome and induces a double strand break. Why does it land on a particular spot? It’s all about the higgelty-piggelty jiggling of proteins in the cellular environment — there isn’t a magic finger telling Spo11 to go to a pre-defined place on the chromosome, it simply does its job wherever it happens to find itself.


You could say the recombination event has a specific cause, the protein complex that cuts and swaps strands of DNA, but the question at hand — why does it recombine at a particular spot in a particular chromosome? — is not specified by any causal agent in the cell. It’s random.


It’s not unscientific. We can study chance processes statistically, no problem. If we threw out all study of chance as unscientific hocus pocus, well, there goes genetics. And epidemiology. And chemistry. And any science that uses statistics. Dang.


Why do they reject chance? One idea that emerged is that they have an excessive faith in causality, and paradoxically, too much trust in the ability of science to give complete, exhaustive explanations for everything.





A deeper and better understanding of DNA will erase the concept of luck/random.



No, it won’t. The more I learn about chemistry and biology, the stronger the value of understanding chance becomes.


I think the idea is that all we have to do is catalog all of the efficient causes to work out every step of an event. Your cancer was caused by a cosmic ray striking and damaging the short arm of your 12th chromosome, creating a defective RAS oncogene. That cosmic ray originated in a supernova 15,000 light years away. That exploding star condensed from a cloud of matter that originated in the Big Bang, so all we have to do is map how every atom, from the beginning of the universe to that detonation in a distant star, and further, every molecular event in the evolution of that RAS oncogene that put it in that particular location on the chromosome, and then every event in your life that led to that cell and your body to be in that specific location to intercept that cosmic ray, we’ll finally understand why you have cancer.


It takes a very deterministic attitude to find that explanation at all satisfying.


No matter how hard we work, we will never have a sufficiently detailed explanation of every feature of the universe to negate the importance of chance. I think quantum physics is also drilling down deep into the nature of how the universe works, and finding that chance plays a role; but even if it were found that the universe is completely deterministic, the complexity of the phenomena and the number of parameters means that those kinds of causes are unknowable, and randomness is a good higher-level description of what is going on.


So get used to it. Why did you get cancer? Bad luck. Chance. But of course, the odds might also have been skewed by inheriting a gene that predisposes you to cancer, or by a poor diet, or by your odd habit of spiking your morning tea with N-ethyl-N-nitrosourea.






from ScienceBlogs http://ift.tt/13T42zV

That paper that proposed that most cancers were due to bad luck, that is, that they were a consequence of biological factors that could not be controlled, has been surprisingly controversial. I thought it was a fairly unsurprising paper that confirmed what we already suspected, but wow, the furious pushback has been something to behold.


Today, though, a couple of MDs have responded to the paper and reinforce what I said.



Steven Novella thinks the general logic is sound.



This is an interesting study and it will be interesting to look at replications and other methods, if they are available, of making the same sort of estimation. What this study suggests is that at least 2/3 of all all cancers are due to random mutations – bad luck. The figure may be higher once breast and prostate cancers are included. Of the remaining third it is not clear how much is due to inherited genes vs lifestyle factors.


The logic of the study is sound, in my opinion. The authors assume that lifestyle and genetic factors affect the risk of tissue specific cancers, but not cancer in general. This study would miss, however, lifestyle or genetic factors that affected the risk of all cancers (regardless of tissue type) equally. One might argue, therefore, that it overestimates the role of random mutations, but that is only if you accept that there are universal risk factors out there.



David Gorski emphasizes that the result actually fits well with prior estimates of the relative contribution of environmental/genetic factors and a probabilistic component.



That cancer is due to a combination of random probabilistic processes, environmental exposures, and heredity is a non-controversial statement. What is controversial are estimates of the relative contribution of environment, given that the percentage of cancers due to inherited cancer-causing mutations is known and low. Take the example of breast cancer, which is a cancer for which environmental and lifestyle contributions are not particularly high, with perhaps 27% of breast cancers being due primarily to environment (which includes diet and exercise, as well as hormone replacement therapy). The vast majority of those environmental contributions come from obesity and alcohol consumption, neither of which reaches the double digits, percentage-wise. Yet there are organizations that promote the idea that “chemicals” in our environment are a major cause of breast cancer. Unfortunately, about 5-10% of breast cancer is inherited, while perhaps up to 27% has a strong environmental component. That leaves around 60% of breast cancer (or, even using higher estimates, at least 50%) as falling into the “we don’t know” or “stochastic” category, with, sadly, nothing that we know of right now that can be done to prevent these cases, while the 10% of hereditary cases can only be prevented by aggressive means, such as chemoprevention or prophylactic surgery.



I still find it interesting, though, that so many people have complained to me about ascribing phenomena to chance — there are some serious misconceptions floating about out there, and I’ve always taken these ideas for granted. I guess I can’t. David Colquhoun and I spent an enlightening afternoon yesterday trying to get through to a few people on Twitter who could not believe we actually thought chance was a reasonable explanation for anything. I did not have the impression that these were anti-science people, or creationists, or anything absurd like that — they just had a striking psychological antipathy to the whole idea of random effects.





no not chance. There must be factors of which we are unaware. U can’t abandon sci. method!






Luck, by definition, has no cause therefore unscientific.






random does not mean without a cause – which is what luck means :-)



Fascinating. Random events are not even scientific? Where did this idea come from? Everything has to have a “cause” of some sort? Weird.


Maybe it’s because a lot of my early training in biology was in genetics, and there you acquire a strong appreciation for the importance of chance events. Genetic gene mapping, for instance, is done by looking at recombination frequencies — the probability that a meiotic crossover event will occur between two genes on the same chromosome, which is a factor of the physical distance separating them. We understand the physical basis of this event, which involves a protein, Spo11, that binds to a random location on the chromosome and induces a double strand break. Why does it land on a particular spot? It’s all about the higgelty-piggelty jiggling of proteins in the cellular environment — there isn’t a magic finger telling Spo11 to go to a pre-defined place on the chromosome, it simply does its job wherever it happens to find itself.


You could say the recombination event has a specific cause, the protein complex that cuts and swaps strands of DNA, but the question at hand — why does it recombine at a particular spot in a particular chromosome? — is not specified by any causal agent in the cell. It’s random.


It’s not unscientific. We can study chance processes statistically, no problem. If we threw out all study of chance as unscientific hocus pocus, well, there goes genetics. And epidemiology. And chemistry. And any science that uses statistics. Dang.


Why do they reject chance? One idea that emerged is that they have an excessive faith in causality, and paradoxically, too much trust in the ability of science to give complete, exhaustive explanations for everything.





A deeper and better understanding of DNA will erase the concept of luck/random.



No, it won’t. The more I learn about chemistry and biology, the stronger the value of understanding chance becomes.


I think the idea is that all we have to do is catalog all of the efficient causes to work out every step of an event. Your cancer was caused by a cosmic ray striking and damaging the short arm of your 12th chromosome, creating a defective RAS oncogene. That cosmic ray originated in a supernova 15,000 light years away. That exploding star condensed from a cloud of matter that originated in the Big Bang, so all we have to do is map how every atom, from the beginning of the universe to that detonation in a distant star, and further, every molecular event in the evolution of that RAS oncogene that put it in that particular location on the chromosome, and then every event in your life that led to that cell and your body to be in that specific location to intercept that cosmic ray, we’ll finally understand why you have cancer.


It takes a very deterministic attitude to find that explanation at all satisfying.


No matter how hard we work, we will never have a sufficiently detailed explanation of every feature of the universe to negate the importance of chance. I think quantum physics is also drilling down deep into the nature of how the universe works, and finding that chance plays a role; but even if it were found that the universe is completely deterministic, the complexity of the phenomena and the number of parameters means that those kinds of causes are unknowable, and randomness is a good higher-level description of what is going on.


So get used to it. Why did you get cancer? Bad luck. Chance. But of course, the odds might also have been skewed by inheriting a gene that predisposes you to cancer, or by a poor diet, or by your odd habit of spiking your morning tea with N-ethyl-N-nitrosourea.






from ScienceBlogs http://ift.tt/13T42zV
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