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The first paper is about blood lipids and CHD and doesn't seem to mention alcohol. Did you post the wrong link?

Whoops, yes. Correcting it now. Thank you. Also updated 2015 to 2014.

Edit: disregard, seeing the updated link you posted.

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If I'm reading correctly, that 2015 MR paper establishes that LDL and triglycerides play a role in heart disease by filtering populations used in prior studies for genetic blood lipid factors. But it doesn't make any claims about alcohol. Is there already a well established link between alcohol and LDL / triglycerides?

My impression is that the relationship between LDL, HDL, and triglycerides and what we eat/drink is not well understood. But I'm not involved in biology or medicine, so maybe you can help me understand this better?

Yes, this is my fault. Sorry about that. Thanks to 'beefman for catching the wrong link, as well.

Thank you very much for that first link. It seems to be severely under-publicised considering the huge amount of exposure that the topic gets.

Do you happen to know if rs1229984 is linked to any particular group that could make this result problematic? I noticed that the paper mentions that "There was also some evidence for a difference in years of education, and, while the size of the effect was small, this requires further investigation." That sounds like a decent-sized red flag.

> Do you happen to know if rs1229984 is linked to any particular group that could make this result problematic?

It seems to me that we would not have to know about the link in order for the conclusions to be unfounded. These MR analyses rest on the assumption that the instrument is not linked to any potential confounders. This seems like a bold and unwarranted assumption when we are talking about an instrument linked to behavior, given the complexity of the chain of events (chemical, biological, and psychological) between gene expression and observable human behavior.

That education red flag involves just one possible confounder out of many that were never considered.

Yes, there is almost always stratification across populations for any chosen marker. You can check out gnomAD for this SNP: http://gnomad.broadinstitute.org/variant/4-100239319-T-C

Take a look at the population frequencies on the right. While the minor allele is infrequent in Europeans, it is extremely common in East Asians, for example.

> 2. While we like to claim that a study randomizing people to alcohol wouldn't be ethical, pre-2014 I don't think that would have been true. I think there was enough equipoise. Post-2014, I would need to see some strong counter-evidence to make me think there is equipoise once again.

That's a very convenient way to socially forbid replication attempts. I don't buy it. The argument basically amounts to a claim that we answered the question definitively in 2014 and anyone questioning that result now is unethical. Today's scientific research, especially in any area pertaining to people, is too unreliable to blindly trust this way.

What's the line? If we found that some intervention group had 90% mortality with the control group having 10% mortality in some experiment, I think you would agree we shouldn't repeat that experiment with a lot of people as you would be randomizing to something likely to kill them. What about 20% mortality to 10%? What about 11% to 10%? What degree of certainty about the results do you need? Obviously there is a line somewhere. But, its not easy, so I wouldn't recommend dismissing such concerns glibly. Is that the same as claiming we answered the question definitively, or is that just ethical research?

We're not talking about administering arsenic to people just in case we're wrong about thousands of years of experience. We're talking about randomizing exposure to an activity that billions of people choose voluntarily, an activity that at worst has an effect of a few parts per 100,000. That's on the same order of risk as being struck by lightning. Unnecessary x-rays are likely worse. Why the outrage over this risk in particular?

Declaring this level of risk to be outside the bounds of permissible research is an attitude incompatible with scientific progress. It's elevating short-term harm prevention to an unjustifiable extreme that makes it impossible to determine whether we have an accurate model of the world.

Sure, you could run an alcohol intervention by an IRB and see what they say. If they think there is equipoise they might go for it. Just because I don't agree doesn't mean I feel strongly about it or would throw down some gauntlet.

I don't accept the legitimacy of IRB rulings; I hope to see a day when these bodies stop blocking research. Researchers are competent to be ethical on their own.

My reading (not just [1], although [1] is a lucid examination) suggests to me that IRBs are net detrimental to research. There's an incentive misalignment that pushes them too far in the "harm" prevention camp and that makes it too difficult to answer scientific questions.

[1] http://slatestarcodex.com/2017/08/29/my-irb-nightmare/

> I don't accept the legitimacy of IRB rulings

That's too bad. The rest of us try to learn something from Nuremberg.

If I am following your logic here, you're saying that because you read a blog post in which a practitioner was surprised at how much more ethically complex it is to conduct scientific research than it is to simply deliver the current state of the art to a patient, you've come to believe that biomedical research should be freed from institutional oversight?

Yes, I think IRBs today do more harm than good. Is that yet another opinion I'm not allowed to express in polite company?

You can express that opinion, but it sounds awfully like you don't understand what your source ("Scott Alexander") was saying, or perhaps that both you and your source don't understand (a) the distinction between practice and research and (b) the relative cultural fixity of institutional reviews in biomedical research versus talk therapy.

So I guess what I'd say is that it looks like the one thing you know about IRBs is that Scott from SlateStarCodex once had a run-in with them and generalized wildly from it.

If I've said something incorrect, refute it. Otherwise, stop it with the vague insinuations. You have no idea what I've read about IRBs and you haven't engaged with any specific arguments in anything I've linked. "It sounds like" is not an argument. It's putting words in someone's mouth.

I'm responding to the argument you actually made, not the variety of arguments you hypothetically could have made. My response has been substantive; I've clearly read the same article you did, as well as your citation. If you're unhappy with your own argument, don't blame me for it.

I think neither of will profit from continuing this discussion, though. You can safely sum up my point as "the problems people in psychology, and the social sciences in general, have with IRBs do not necessarily generalize to biomedical research". One of the basic complaints scientists have about IRBs is the "mission creep" from human medical research to the rest of the sciences. The premise of that argument doesn't line up with your argument here on this thread.

Also, SlateStarCodex is bad.

You are not in fact responding to any argument I've made.

My point is that IRBs have an incentive structure that encourages excessive risk aversion. My citation is an instance of this phenomenon in action. It has nothing to do with the particulars of psychology. You have not attempted to address this incentive alignment argument in any way. Blocking an attempt to replicate an alcohol study due to weak evidence for a very small negative effect is another example, albeit hypothetical, of this same excessive risk aversion. You have not made a similarly substantial argument. Instead, you've just asserted that institutional review is embedded in biomedical research. It is, but I think it shouldn't be.

> Also, SlateStarCodex is bad.

It's amazing that immediately after a paragraph in which you claim to be making a substantive argument, you make a bald and unsupported assertion that an influential and widely-read blog, one that Pinker has called "wonderful", is in fact "bad".

This is not the kind of intellectual conversation that HN was meant to host.

>There may be something about alcohol that was helpful in the 1950s that is no longer so today, due to these environmental changes.

Maybe an interaction with the prevalence of leaded gasoline?

Does ASA stand for Alcohol Septal Ablation?

In this case, ASA is Aspirin.

I am surprised that taking a baby aspirin every day may turn out to be harmful. It's been common wisdom for years, and now it may (or may not) be wrong. Like the advice that chocolate and red wine is good for you.

Why would taking a drug everyday not seem like it could have some obvious concequences?

I remember reading a paper some time ago claiming a relationship between NSAID use and kidney cancer. And then one about Aspirin use and lower risk of colon cancer. The side effects of Aspirin are not just the risk of stomach bleeding as stated on the package.

If some drug was unconditionally good for us, why haven't our bodies evolved to secrete that drug on their own?