12 ms·

Alcohol, health, and the ruthless logic of the Asian flush

137 points by spekcular 5y ago

acenes 5y ago
"The simplest explanation is that these genes are adaptive." Really? That's the simplest explanation? https://royalsocietypublishing.org/doi/10.1098/rspb.1979.0086 https://royalsocietypublishing.org/doi/10.1098/rspb.1979.008...
Rebelgecko 5y ago
One thing that I found interesting is the implication that a strong negative reaction to alcohol is something that evolved as a response to alcoholic beverages being first created in Asia. Is there any way to study the prevalence of the ADH1B and ADH1C genes over time? e.g. to determine if they actually become more common as alcoholic beverages proliferated?
- didibus 5y ago
  I was a bit bothered by this part, because the article didn't seem transparent in saying that this is only a hypothesis, and instead kind of talked about it as a well established proven fact.
  - fastball 5y ago
    Eh, the crux of the article doesn't really rely on said hypothesis so I don't think the author was really trying to pull a fast one on anyone.
- xyzzyz 5y ago
  Yes, you can get DNA from human remains, even very old ones.
  - Rebelgecko 5y ago
    Has anyone tried that for these particular genes?
methbed123 5y ago
In the grim far future, instead of an interlock device on your car after a DWI, how about some gene therapy to vaccinate against alcoholism via alcohol dehydrogenase?
- torgian 5y ago
  Man, that sounds like a crappy future for alcohol.
  - ultrarunner 5y ago
    Broke: forced sterilization Woke: forced gene therapy to disincentivize undesirable behavior. (I note that another article on the front page is entitled "The most precious resource is agency", though I haven' gotten to it quite yet).
  - fy20 5y ago
    It'll just push the alcohol industry to invent synthehol.
    - Gibbon1 5y ago
      I saw a post by a guy getting his masters in chemistry who mentioned two or three drugs that each mimicked part of the effects of alcohol. Week later he took the post down.
      - corin_ 5y ago
        There are plenty of well known drugs, some illegal without a prescription some illegal entirely, which mimic parts of alcohol's effects. For example GHB https://en.wikipedia.org/wiki/Gamma-Hydroxybutyric_acid https://en.wikipedia.org/wiki/Gamma-Hydroxybutyric_acid There are also attempts to specifically create drugs that will be identical to alcohol but without the negatives. Whether that will ever come to fruition, and be legal, I don't know. For example https://www.menshealth.com/uk/nutrition/a30117412/alcohol-hangover-alcarelle/ https://www.menshealth.com/uk/nutrition/a30117412/alcohol-ha...
didibus 5y ago
I think another likely reason why disulfiram might not work is that the hypothesis is wrong, and the gene variant is only correlated with alcoholism, but might not be the cause of why there are lower rate of alcoholism in people with it.
- vintermann 5y ago
  Well, we know that 1. People with the gene variant drink slightly less than people without it, but otherwise their drinking patterns follows everyone else's. 2. alcoholism does not cause the gene variant in individuals (obviously). 3. The gene variant is invisible. Within a reasonable population group, it seems basically random who carries it or not (I.e, you can predict that Koreans are more likely to carry it than Americans, but within a group of Americans, or a group of Koreans, it's basically impossible to guess who carries it or not). It's even been used for Mendelian randomization studies, because as far as we can tell, it affects nothing else than alcohol digestion. A better explanation for the relative lack of success of disulfiram is that you don't take it from birth without choosing to. You have to want to take it to gain the benefit of it, but if you need it, you don't really want to take it. You want to drink. It's the big problem of addiction, you want things that contradict each other, and you want the bad things more. The drug researcher and philosopher Ole-Jørgen Skog wrote a lot of interesting things on this topic, on "The weakness of will" and time preferences: "If the consumer's sole motive for changing his level of patience is to escape an allocation that is dictated by his first order preference (including time preference), but that contradicts his second order preferences, he will not be able to achieve this by rational means. This is to put the cart before the horse." (But he thought that if you sought patience for its own sake, rather for the sake of not wanting to be an alcoholic, there was maybe a way. Since deciding to value patience for its own sake is not strictly speaking a rational decision.)
  - didibus 5y ago
    > A better explanation for the relative lack of success of disulfiram is that you don't take it from birth without choosing to. You have to want to take it to gain the benefit of it, but if you need it, you don't really want to take it. You want to drink. It's the big problem of addiction, you want things that contradict each other, and you want the bad things more. I don't see what supports this being a better explanation, I feel at this point all explanation that fits the data are equally likely, otherwise it's just bias. In fact, I would say the proposed model failed the first test, which is that a good model should be good at predicting outcomes. In this case, the model failed to predict the outcome, as causing the condition in people did not reduce their alcohol consumption as we expected from the model. Sure, it could be that only some details of the model are wrong, like that the condition only works if established prior to a history of alcohol consumption, or that it only works if having no choice on the matter of the condition, etc. But at this point it seems just as likely that the condition might not be the cause, but only correlated in possibly another way. For example, we might have it backwards, and it is the lower drive to consume alcohol which caused the gene variant in the fist place.
sho 5y ago
Summary: East asians are partially adapted against alcohol because they invented it first and alcohol reduces fitness. No evidence presented but it sounds cute. Presumably they are also adapted against milk because of reasons.
- deleted 5y ago
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- caymanjim 5y ago
  I think it's the other way around with milk. Almost all mammals lose the ability to digest lactose in adulthood. Europeans slowly evolved to tolerate it, presumably because of widespread reliance on cows, sheep, and goats. It's a beneficial adaptation; milk is super-nutritious, and those animals convert indigestible grasses into digestible milk in environments where crops only grow for half the year.
  - sumedh 5y ago
    Milk is pretty big in India but I have read that majority of Indians are lactose intolerant. So its a bit weird that lactose intolerant population uses milk heavily in its diet.
    - edwcross 5y ago
      I can't speak for milk itself, but ghee (which is often used in India), for instance, is virtually lactose-free, so even lactose intolerant people can eat it. That also happens with cheese and other dairy products; so they are not entirely incompatible.
    - thaumasiotes 5y ago
      Milk is available and regularly purchased in every Chinese store. More than 90% of them are lactose intolerant. It's not entirely clear to me why they drink so much of it, but I believe they consider it health food. It probably comes from copying Europeans. (Do note that milk is quite nutritious even when you can't digest the lactose. The problem isn't that the milk isn't nutritious -- the problem is that the lactose will cause you various problems, most notably diarrhea.)
durpkingOP 5y ago
[delete post]
kergonath 5y ago
That’s very truthy, but there’s quite a bit of jumping to conclusions and correlation-causation issues there.
methbed123 5y ago
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797030/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797030/
nl 5y ago
This makes little sense. Sure, maybe alcohol was invented first in China (that's the earliest we have found anyway). But we have found usage in ancient Persia from less than 2000 years after China. If this gene is highly selective, why wasn't it also equally selective outside East Asia? A more likely explanation is that it is a random variation and provides little to no evolutionary benefit.
- nsomaru 5y ago
  If it was random, why did it become dominant if it provided no evolutionary advantage? There’s variations going on all the time, maybe they’re random, maybe they’re not. But the ones that stick in a population are the ones that get selected by outcompeting hosts without the variation.
  - AstralStorm 5y ago
    You could probably also ask why Temujin had many children. Founder effects are a thing and a sufficient explanation. They hold even for relatively detrimental defects, and likely hold even better for something as silent as acetaldehyde metabolism.
  - nl 5y ago
    > There’s variations going on all the time, maybe they’re random, maybe they’re not. But the ones that stick in a population are the ones that get selected by outcompeting hosts without the variation. This is only true if there is correlation between the variation and survival in terms of breeding. A good example is the high incidence of Haemophilia B in European royalty[1]. It certainly doesn't give any selective advantage, but the fact that royalty are more likely to get medical care means it doesn't have any selective disadvantage either. There are plenty of other random variations that aren't selective. Eye colour, male pattern baldness, the range of earlobe attachedness[2] are all variations that don't have any selective pressure and so their appearance in various geographic areas is down to history rather genetics. Edit: Another comment led me to a paper arguing compellingly that this gene provided some protection against diseases carried in mouldy rice, and that was selective in China. See further discussion here: https://news.ycombinator.com/item?id=27705633 https://news.ycombinator.com/item?id=27705633 [1] https://en.wikipedia.org/wiki/Haemophilia_in_European_royalty https://en.wikipedia.org/wiki/Haemophilia_in_European_royalt... [2] https://en.wikipedia.org/wiki/Earlobe#Genetics https://en.wikipedia.org/wiki/Earlobe#Genetics
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d--b 5y ago
This feels completely anachronistic. For early humans to evolve genes that prevent them from getting drunk, you’d assume that a large proportion of people would have to die or become infertile from alcoholism. Given the number of things people would die of, the slow speed of progression of alcohol-related diseases, and the difficulty of producing enough beer for it to become a evolution-wise health problem, the conclusion really sounds like a stretch.
- 6510 5y ago
  Die or reproduce faster.
- PicassoCTs 5y ago
  Seems being unable to waste yourself 247 is selected for by the opposite sex?
- dividedbyzero 5y ago
  Beer is pretty easy to make if you're in an early agrarian state with a modest surplus of cereals, not up to the standards of modern-day breweries, but good enough by a fair margin. IIRC if you were a temple worker in the ancient state of Uruk, your pay would have included a bowl of beer a day. Such arrangements weren't rare. Historically, people have drunk surprising amounts of alcohol – we may not have been as collectively sober as today for millennia (depending on the exact location, to be sure); beer and wine have the big advantage that they're reasonably safe to drink even if the primary source of water isn't (due to the fermentation process and the alcohol content), and that it's easier to tell when they aren't (because if fermentation doesn't work right, you definitely notice). In some of the more remote areas in the alps, even children still drank lots of diluted wine as late as the 1950s, for precisely that reason. That sort of thing was the rule, not the exception, for Europe pre-industrialization. Evolutionary pressure on humans also doesn't usually involve everyone with allele X dropping dead right away, because people are pretty creative at avoiding that outcome, and it's often (probably, likely) not about small-ish effects under good, stable conditions, but outsize ones in exceptional circumstances. There have been bad years and very bad years all the time; even as late as the 19th century, agrarian societies were pretty much helpless if harvests failed on a large scale (think Irish Potato Famine), and that's after 6000-ish years of working on that existential problem. When bad years become bad decades, and lots and lots of people die, that's when things like alcohol tolerance and lactose tolerance can make a big difference. Being able to tolerate alcohol may mean access to a cleaner source of fluid, less pathogens for weakened immune systems to deal with, and access to nutrients that store pretty well. There may have been a social component as well – getting drunk together has been an extremely important vehicle for networking and bonding for literal ages. Finally, being able to get drunk relatively safely may have kept people functioning through highly traumatic experiences as well. Not saying that's what happened for sure, but a few ways this could have played a decisive role.
wodenokoto 5y ago
The article ends up being a very roundabout way of saying “curing alcoholism is hard even with Antabuse”.
vanderZwan 5y ago
Tangent: a pet peeve of mine is plots of alcohol vs disease plots that suggest that one or two drinks a day is healthier than none. This is not the case. The data sets that produce these plots almost never take into account why people stop drinking. When you do control for this, and in the process filter out people who stop drinking because of other severe health issues, it becomes obvious that not drinking at all is the healthiest option.
- jasode 5y ago
  >The data sets that produce these plots almost never take into account why people stop drinking. When you do control for this, and in the process filter out people who stop drinking because of other severe health issues, it becomes obvious that not drinking at all is the healthiest option. But many studies do account for that scenario of "sick quitters". The statistical correlation still showed that light moderate drinkers had lower mortality rates. The study itself may still be flawed but the point is that the researchers were aware of "sick quitters" being categorized as "non-drinkers" and thus distorting the results. Excerpt from 90+ Study publication https://pubmed.ncbi.nlm.nih.gov/17350977/ https://pubmed.ncbi.nlm.nih.gov/17350977/ : >The greater proportion of surviving participants in our study who reported not drinking at follow-up compared to baseline is probably due to a combination of the cohort’s becoming older and drinking less, secular changes in alcohol consumption with time, and survival selection effects. Decline in consumption is also associated with the development of ill health, particularly cardiovascular disease. This accumulation of ill health and higher mortality risk in ‘sick quitters’ increases the observed benefit in drinkers if non-drinkers include these ex-drinkers [6, 24, 26]. In addition, regular light drinkers tend to have characteristics advantageous to health [26, 27]. Thus, controlling for baseline disease is important, particularly if alcohol history is unknown. With adjustment for baseline medical history as well as body mass index, exercise, and smoking, the lower risks of death among light and moderate alcohol drinkers observed in our study did not change substantially and remained statistically significant although those associated with heavier drinking were reduced.
  - vintermann 5y ago
    Yes, it was back and forth many years whether the dip at the bottom (with very modest drinkers being slightly healthier than non-drinkers) was genuine, or whether there was some remaining effect which hadn't been appropriately controlled for. But that was pretty much settled with Mendelian Randomization studies on exactly this gene. As the article says, some people have different versions of the alcohol dehydrogenase enzyme, which basically gives them a worse hangover, faster. People with this condition drink slightly less than they otherwise would, wherever they are on the consumption curve. Knowing that, and knowing that the gene is more or less randomly distributed in the population under study, and assuming the gene affects nothing else (a safe bet, since alcohol dehydrogenase is a fairly task-specific enzyme), we can disentangle the effect of the alcohol from all the other things that could cause you to drink more or less alcohol. Now the consensus seems pretty solidly on that the apparent protective effect of moderate alcohol consumption on stroke, cancer or heart disease is non-causal.
H8crilA 5y ago
So much negativity in the comments here on the subtopic on "what caused the evolution". Yes, we know that nobody really knows, the author doesn't really know either. What the post conceptually centers on is best depicted in that chart in the middle. Also, if you read the entire thing you'd have found out that the author isn't trying to make any specific point, but rather is telling a story.
misja111 5y ago
Another interesting fact not mentioned in the article, is that men produce way more ADH than women: https://sites.duke.edu/apep/module-1-gender-matters/content/content-gender-differences-in-alcohol-metabolism/#:~:text=Males%20and%20females%20differ%20in,their%20stomach%20and%20their%20liver https://sites.duke.edu/apep/module-1-gender-matters/content/.... I wonder how that fits into the author's narrative?
- dynm 5y ago
  (author here) I did not know that, and I'm not sure how it fits in! All else being equal, more ADH would imply faster acetaldehyde buildup, meaning men would have more of a "flush" than women. I don't know if all else is equal, though. For example, if men also had more ALDH, then they'd also be able to break down that acetaldehyde into acetate faster. Taking a quick glance at the literature, it's... super complicated. This paper (https://doi.org/10.1002/jcla.10076 https://doi.org/10.1002/jcla.10076) suggests that women have lower gastric ADH but higher liver ADH. There's some animal studies that suggest men have higher ALDH, but also some contradictory human studies that suggest that everything is just the same. Argh, biology.
RandomLensman 5y ago
I always though the basic hypothesis is the other way around: the populations with low alcohol tolerance used methods other than brewing to generate safe water (e.g., boiling as in tea) and hence no selection for alcohol tolerance. If there really is a selection against alcohol, why did that not kick in outside Asia, too? The selection mechanism postulated would need to be fast... are 2k years or so really significant?
- eythian 5y ago
  > If there really is a selection against alcohol, why did that not kick in outside Asia, too? Evolution isn't a perfect machine. If those variant genes don't pop up at the right place at the right time, they might just not happen to catch on.
jaqalopes 5y ago
Cannot relate to people trying to "well, actually" this article based on their absolute certainty that evolution happened the way it did for a specific reason (a thing we can never actually prove). The point of the post is to tell an interesting story and the writing is fun and funny. Lighten up people, sheesh.
- zazen 5y ago
  So many internet know-it-alls thinking they'll disprove the entire article all at once with their one-sentence intellectual zinger, and then we'll all bow down and praise them for their great cleverness. I despair of internet forums - some have better culture for a while, but as far as I've seen, Dunning-Kruger always wins in the end.
sgt101 5y ago
The thing is that too consume alcohol at a harmful level you pretty well need distillation, which only came in about eight hundred years ago, so this doesn't leave much room for evolution!
- rscho 5y ago
  Absolutely not. You can kill yourself with beer just fine over the years.
- zazen 5y ago
  You can't be an alcoholic using wine / beer? How did you get to that conclusion?
- machello13 5y ago
  Uh, what? People have been killing themselves with alcohol for thousands of years.
- thehappypm 5y ago
  Plenty of college kids get hospitalized drinking 4% beer.
lgvln 5y ago
Intriguing idea but not sure if it holds up upon further scrutiny. Alcoholic drinks have been around since at least as early as the Neolithic period (10,000BCE) and the earliest archaeological evidence shows that they have been around in China and Middle East/Mesopotamia around the same time (~7000BCE). So why did the East Asians evolved to have the "Asian flush" while the rest of the world didn't? Someone mentioned that alcoholic drinks were safer to drink than water so people were drinking alcoholic drinks as a safer alternative. But we have to remember the various "cradles of civilizations"(Mesopotamia, Yellow river, Indus Valley etc) all evolved around rivers so access to clean water probably wasn't a major issue. What's more likely is the effect is an unintended consequence. Other qualities "unique" to Asians or East Asians are a general lack of body hair and (more pronounced) neoteny. I don't think there are adequate theories for those quality either. There's still a long way to go to fully understand evolution and genetics.
- BurningFrog 5y ago
  China has had continuous organized civilization, and the alcohol it produces, at least as long as anywhere. That makes a good environment for mutations that protect people from alcohol consumption, but such mutations still has to randomly appear, and that it happened to appear in East Asia is probably just random. The fact that populations who have never had alcohol succumb to rampant alcoholism when first getting access implies that even the eurasian populations without the Asian Flush genes probably has some less obvious genetic protection. You can also think of it as the most alcoholic prone genes have been weeded out over the centuries.
- rrrrrrrrrrrryan 5y ago
  It's tea. Early European civilisations kept their water safe by making it lightly alcoholic - Early Asian civilizations just boiled their water to make tea.
chansiky 5y ago
To be fair, Asian flush is a terrific excuse for sobriety, and I’m glad to have it.

137 points by spekcular 5y ago

"The simplest explanation is that these genes are adaptive." Really? That's the simplest explanation? https://royalsocietypublishing.org/doi/10.1098/rspb.1979.0086 https://royalsocietypublishing.org/doi/10.1098/rspb.1979.008...

Rebelgecko 5y ago

One thing that I found interesting is the implication that a strong negative reaction to alcohol is something that evolved as a response to alcoholic beverages being first created in Asia. Is there any way to study the prevalence of the ADH1B and ADH1C genes over time? e.g. to determine if they actually become more common as alcoholic beverages proliferated?

didibus 5y ago
I was a bit bothered by this part, because the article didn't seem transparent in saying that this is only a hypothesis, and instead kind of talked about it as a well established proven fact.
- fastball 5y ago
  Eh, the crux of the article doesn't really rely on said hypothesis so I don't think the author was really trying to pull a fast one on anyone.
xyzzyz 5y ago
Yes, you can get DNA from human remains, even very old ones.
- Rebelgecko 5y ago
  Has anyone tried that for these particular genes?

methbed123 5y ago

In the grim far future, instead of an interlock device on your car after a DWI, how about some gene therapy to vaccinate against alcoholism via alcohol dehydrogenase?

torgian 5y ago
Man, that sounds like a crappy future for alcohol.
- ultrarunner 5y ago
  Broke: forced sterilization Woke: forced gene therapy to disincentivize undesirable behavior. (I note that another article on the front page is entitled "The most precious resource is agency", though I haven' gotten to it quite yet).
- fy20 5y ago
  It'll just push the alcohol industry to invent synthehol.
  - Gibbon1 5y ago
    I saw a post by a guy getting his masters in chemistry who mentioned two or three drugs that each mimicked part of the effects of alcohol. Week later he took the post down.
    - corin_ 5y ago
      There are plenty of well known drugs, some illegal without a prescription some illegal entirely, which mimic parts of alcohol's effects. For example GHB https://en.wikipedia.org/wiki/Gamma-Hydroxybutyric_acid https://en.wikipedia.org/wiki/Gamma-Hydroxybutyric_acid There are also attempts to specifically create drugs that will be identical to alcohol but without the negatives. Whether that will ever come to fruition, and be legal, I don't know. For example https://www.menshealth.com/uk/nutrition/a30117412/alcohol-hangover-alcarelle/ https://www.menshealth.com/uk/nutrition/a30117412/alcohol-ha...

didibus 5y ago

I think another likely reason why disulfiram might not work is that the hypothesis is wrong, and the gene variant is only correlated with alcoholism, but might not be the cause of why there are lower rate of alcoholism in people with it.

vintermann 5y ago
Well, we know that 1. People with the gene variant drink slightly less than people without it, but otherwise their drinking patterns follows everyone else's. 2. alcoholism does not cause the gene variant in individuals (obviously). 3. The gene variant is invisible. Within a reasonable population group, it seems basically random who carries it or not (I.e, you can predict that Koreans are more likely to carry it than Americans, but within a group of Americans, or a group of Koreans, it's basically impossible to guess who carries it or not). It's even been used for Mendelian randomization studies, because as far as we can tell, it affects nothing else than alcohol digestion. A better explanation for the relative lack of success of disulfiram is that you don't take it from birth without choosing to. You have to want to take it to gain the benefit of it, but if you need it, you don't really want to take it. You want to drink. It's the big problem of addiction, you want things that contradict each other, and you want the bad things more. The drug researcher and philosopher Ole-Jørgen Skog wrote a lot of interesting things on this topic, on "The weakness of will" and time preferences: "If the consumer's sole motive for changing his level of patience is to escape an allocation that is dictated by his first order preference (including time preference), but that contradicts his second order preferences, he will not be able to achieve this by rational means. This is to put the cart before the horse." (But he thought that if you sought patience for its own sake, rather for the sake of not wanting to be an alcoholic, there was maybe a way. Since deciding to value patience for its own sake is not strictly speaking a rational decision.)
- didibus 5y ago
  > A better explanation for the relative lack of success of disulfiram is that you don't take it from birth without choosing to. You have to want to take it to gain the benefit of it, but if you need it, you don't really want to take it. You want to drink. It's the big problem of addiction, you want things that contradict each other, and you want the bad things more. I don't see what supports this being a better explanation, I feel at this point all explanation that fits the data are equally likely, otherwise it's just bias. In fact, I would say the proposed model failed the first test, which is that a good model should be good at predicting outcomes. In this case, the model failed to predict the outcome, as causing the condition in people did not reduce their alcohol consumption as we expected from the model. Sure, it could be that only some details of the model are wrong, like that the condition only works if established prior to a history of alcohol consumption, or that it only works if having no choice on the matter of the condition, etc. But at this point it seems just as likely that the condition might not be the cause, but only correlated in possibly another way. For example, we might have it backwards, and it is the lower drive to consume alcohol which caused the gene variant in the fist place.

sho 5y ago

Summary: East asians are partially adapted against alcohol because they invented it first and alcohol reduces fitness. No evidence presented but it sounds cute. Presumably they are also adapted against milk because of reasons.

deleted 5y ago
[deleted]
caymanjim 5y ago
I think it's the other way around with milk. Almost all mammals lose the ability to digest lactose in adulthood. Europeans slowly evolved to tolerate it, presumably because of widespread reliance on cows, sheep, and goats. It's a beneficial adaptation; milk is super-nutritious, and those animals convert indigestible grasses into digestible milk in environments where crops only grow for half the year.
- sumedh 5y ago
  Milk is pretty big in India but I have read that majority of Indians are lactose intolerant. So its a bit weird that lactose intolerant population uses milk heavily in its diet.
  - edwcross 5y ago
    I can't speak for milk itself, but ghee (which is often used in India), for instance, is virtually lactose-free, so even lactose intolerant people can eat it. That also happens with cheese and other dairy products; so they are not entirely incompatible.
  - thaumasiotes 5y ago
    Milk is available and regularly purchased in every Chinese store. More than 90% of them are lactose intolerant. It's not entirely clear to me why they drink so much of it, but I believe they consider it health food. It probably comes from copying Europeans. (Do note that milk is quite nutritious even when you can't digest the lactose. The problem isn't that the milk isn't nutritious -- the problem is that the lactose will cause you various problems, most notably diarrhea.)

durpkingOP 5y ago

[delete post]

kergonath 5y ago

That’s very truthy, but there’s quite a bit of jumping to conclusions and correlation-causation issues there.

methbed123 5y ago

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797030/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797030/

nl 5y ago

This makes little sense. Sure, maybe alcohol was invented first in China (that's the earliest we have found anyway). But we have found usage in ancient Persia from less than 2000 years after China. If this gene is highly selective, why wasn't it also equally selective outside East Asia? A more likely explanation is that it is a random variation and provides little to no evolutionary benefit.

nsomaru 5y ago
If it was random, why did it become dominant if it provided no evolutionary advantage? There’s variations going on all the time, maybe they’re random, maybe they’re not. But the ones that stick in a population are the ones that get selected by outcompeting hosts without the variation.
- AstralStorm 5y ago
  You could probably also ask why Temujin had many children. Founder effects are a thing and a sufficient explanation. They hold even for relatively detrimental defects, and likely hold even better for something as silent as acetaldehyde metabolism.
- nl 5y ago
  > There’s variations going on all the time, maybe they’re random, maybe they’re not. But the ones that stick in a population are the ones that get selected by outcompeting hosts without the variation. This is only true if there is correlation between the variation and survival in terms of breeding. A good example is the high incidence of Haemophilia B in European royalty[1]. It certainly doesn't give any selective advantage, but the fact that royalty are more likely to get medical care means it doesn't have any selective disadvantage either. There are plenty of other random variations that aren't selective. Eye colour, male pattern baldness, the range of earlobe attachedness[2] are all variations that don't have any selective pressure and so their appearance in various geographic areas is down to history rather genetics. Edit: Another comment led me to a paper arguing compellingly that this gene provided some protection against diseases carried in mouldy rice, and that was selective in China. See further discussion here: https://news.ycombinator.com/item?id=27705633 https://news.ycombinator.com/item?id=27705633 [1] https://en.wikipedia.org/wiki/Haemophilia_in_European_royalty https://en.wikipedia.org/wiki/Haemophilia_in_European_royalt... [2] https://en.wikipedia.org/wiki/Earlobe#Genetics https://en.wikipedia.org/wiki/Earlobe#Genetics

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d--b 5y ago

This feels completely anachronistic. For early humans to evolve genes that prevent them from getting drunk, you’d assume that a large proportion of people would have to die or become infertile from alcoholism. Given the number of things people would die of, the slow speed of progression of alcohol-related diseases, and the difficulty of producing enough beer for it to become a evolution-wise health problem, the conclusion really sounds like a stretch.

6510 5y ago
Die or reproduce faster.
PicassoCTs 5y ago
Seems being unable to waste yourself 247 is selected for by the opposite sex?
dividedbyzero 5y ago
Beer is pretty easy to make if you're in an early agrarian state with a modest surplus of cereals, not up to the standards of modern-day breweries, but good enough by a fair margin. IIRC if you were a temple worker in the ancient state of Uruk, your pay would have included a bowl of beer a day. Such arrangements weren't rare. Historically, people have drunk surprising amounts of alcohol – we may not have been as collectively sober as today for millennia (depending on the exact location, to be sure); beer and wine have the big advantage that they're reasonably safe to drink even if the primary source of water isn't (due to the fermentation process and the alcohol content), and that it's easier to tell when they aren't (because if fermentation doesn't work right, you definitely notice). In some of the more remote areas in the alps, even children still drank lots of diluted wine as late as the 1950s, for precisely that reason. That sort of thing was the rule, not the exception, for Europe pre-industrialization. Evolutionary pressure on humans also doesn't usually involve everyone with allele X dropping dead right away, because people are pretty creative at avoiding that outcome, and it's often (probably, likely) not about small-ish effects under good, stable conditions, but outsize ones in exceptional circumstances. There have been bad years and very bad years all the time; even as late as the 19th century, agrarian societies were pretty much helpless if harvests failed on a large scale (think Irish Potato Famine), and that's after 6000-ish years of working on that existential problem. When bad years become bad decades, and lots and lots of people die, that's when things like alcohol tolerance and lactose tolerance can make a big difference. Being able to tolerate alcohol may mean access to a cleaner source of fluid, less pathogens for weakened immune systems to deal with, and access to nutrients that store pretty well. There may have been a social component as well – getting drunk together has been an extremely important vehicle for networking and bonding for literal ages. Finally, being able to get drunk relatively safely may have kept people functioning through highly traumatic experiences as well. Not saying that's what happened for sure, but a few ways this could have played a decisive role.

wodenokoto 5y ago

The article ends up being a very roundabout way of saying “curing alcoholism is hard even with Antabuse”.

vanderZwan 5y ago

Tangent: a pet peeve of mine is plots of alcohol vs disease plots that suggest that one or two drinks a day is healthier than none. This is not the case. The data sets that produce these plots almost never take into account why people stop drinking. When you do control for this, and in the process filter out people who stop drinking because of other severe health issues, it becomes obvious that not drinking at all is the healthiest option.

jasode 5y ago
>The data sets that produce these plots almost never take into account why people stop drinking. When you do control for this, and in the process filter out people who stop drinking because of other severe health issues, it becomes obvious that not drinking at all is the healthiest option. But many studies do account for that scenario of "sick quitters". The statistical correlation still showed that light moderate drinkers had lower mortality rates. The study itself may still be flawed but the point is that the researchers were aware of "sick quitters" being categorized as "non-drinkers" and thus distorting the results. Excerpt from 90+ Study publication https://pubmed.ncbi.nlm.nih.gov/17350977/ https://pubmed.ncbi.nlm.nih.gov/17350977/ : >The greater proportion of surviving participants in our study who reported not drinking at follow-up compared to baseline is probably due to a combination of the cohort’s becoming older and drinking less, secular changes in alcohol consumption with time, and survival selection effects. Decline in consumption is also associated with the development of ill health, particularly cardiovascular disease. This accumulation of ill health and higher mortality risk in ‘sick quitters’ increases the observed benefit in drinkers if non-drinkers include these ex-drinkers [6, 24, 26]. In addition, regular light drinkers tend to have characteristics advantageous to health [26, 27]. Thus, controlling for baseline disease is important, particularly if alcohol history is unknown. With adjustment for baseline medical history as well as body mass index, exercise, and smoking, the lower risks of death among light and moderate alcohol drinkers observed in our study did not change substantially and remained statistically significant although those associated with heavier drinking were reduced.
- vintermann 5y ago
  Yes, it was back and forth many years whether the dip at the bottom (with very modest drinkers being slightly healthier than non-drinkers) was genuine, or whether there was some remaining effect which hadn't been appropriately controlled for. But that was pretty much settled with Mendelian Randomization studies on exactly this gene. As the article says, some people have different versions of the alcohol dehydrogenase enzyme, which basically gives them a worse hangover, faster. People with this condition drink slightly less than they otherwise would, wherever they are on the consumption curve. Knowing that, and knowing that the gene is more or less randomly distributed in the population under study, and assuming the gene affects nothing else (a safe bet, since alcohol dehydrogenase is a fairly task-specific enzyme), we can disentangle the effect of the alcohol from all the other things that could cause you to drink more or less alcohol. Now the consensus seems pretty solidly on that the apparent protective effect of moderate alcohol consumption on stroke, cancer or heart disease is non-causal.

H8crilA 5y ago

So much negativity in the comments here on the subtopic on "what caused the evolution". Yes, we know that nobody really knows, the author doesn't really know either. What the post conceptually centers on is best depicted in that chart in the middle. Also, if you read the entire thing you'd have found out that the author isn't trying to make any specific point, but rather is telling a story.

misja111 5y ago

Another interesting fact not mentioned in the article, is that men produce way more ADH than women: https://sites.duke.edu/apep/module-1-gender-matters/content/content-gender-differences-in-alcohol-metabolism/#:~:text=Males%20and%20females%20differ%20in,their%20stomach%20and%20their%20liver https://sites.duke.edu/apep/module-1-gender-matters/content/.... I wonder how that fits into the author's narrative?

dynm 5y ago
(author here) I did not know that, and I'm not sure how it fits in! All else being equal, more ADH would imply faster acetaldehyde buildup, meaning men would have more of a "flush" than women. I don't know if all else is equal, though. For example, if men also had more ALDH, then they'd also be able to break down that acetaldehyde into acetate faster. Taking a quick glance at the literature, it's... super complicated. This paper (https://doi.org/10.1002/jcla.10076 https://doi.org/10.1002/jcla.10076) suggests that women have lower gastric ADH but higher liver ADH. There's some animal studies that suggest men have higher ALDH, but also some contradictory human studies that suggest that everything is just the same. Argh, biology.

RandomLensman 5y ago

I always though the basic hypothesis is the other way around: the populations with low alcohol tolerance used methods other than brewing to generate safe water (e.g., boiling as in tea) and hence no selection for alcohol tolerance. If there really is a selection against alcohol, why did that not kick in outside Asia, too? The selection mechanism postulated would need to be fast... are 2k years or so really significant?

eythian 5y ago
> If there really is a selection against alcohol, why did that not kick in outside Asia, too? Evolution isn't a perfect machine. If those variant genes don't pop up at the right place at the right time, they might just not happen to catch on.

jaqalopes 5y ago

Cannot relate to people trying to "well, actually" this article based on their absolute certainty that evolution happened the way it did for a specific reason (a thing we can never actually prove). The point of the post is to tell an interesting story and the writing is fun and funny. Lighten up people, sheesh.

zazen 5y ago
So many internet know-it-alls thinking they'll disprove the entire article all at once with their one-sentence intellectual zinger, and then we'll all bow down and praise them for their great cleverness. I despair of internet forums - some have better culture for a while, but as far as I've seen, Dunning-Kruger always wins in the end.

sgt101 5y ago

The thing is that too consume alcohol at a harmful level you pretty well need distillation, which only came in about eight hundred years ago, so this doesn't leave much room for evolution!

rscho 5y ago
Absolutely not. You can kill yourself with beer just fine over the years.
zazen 5y ago
You can't be an alcoholic using wine / beer? How did you get to that conclusion?
machello13 5y ago
Uh, what? People have been killing themselves with alcohol for thousands of years.
thehappypm 5y ago
Plenty of college kids get hospitalized drinking 4% beer.

lgvln 5y ago

Intriguing idea but not sure if it holds up upon further scrutiny. Alcoholic drinks have been around since at least as early as the Neolithic period (10,000BCE) and the earliest archaeological evidence shows that they have been around in China and Middle East/Mesopotamia around the same time (~7000BCE). So why did the East Asians evolved to have the "Asian flush" while the rest of the world didn't? Someone mentioned that alcoholic drinks were safer to drink than water so people were drinking alcoholic drinks as a safer alternative. But we have to remember the various "cradles of civilizations"(Mesopotamia, Yellow river, Indus Valley etc) all evolved around rivers so access to clean water probably wasn't a major issue. What's more likely is the effect is an unintended consequence. Other qualities "unique" to Asians or East Asians are a general lack of body hair and (more pronounced) neoteny. I don't think there are adequate theories for those quality either. There's still a long way to go to fully understand evolution and genetics.

BurningFrog 5y ago
China has had continuous organized civilization, and the alcohol it produces, at least as long as anywhere. That makes a good environment for mutations that protect people from alcohol consumption, but such mutations still has to randomly appear, and that it happened to appear in East Asia is probably just random. The fact that populations who have never had alcohol succumb to rampant alcoholism when first getting access implies that even the eurasian populations without the Asian Flush genes probably has some less obvious genetic protection. You can also think of it as the most alcoholic prone genes have been weeded out over the centuries.
rrrrrrrrrrrryan 5y ago
It's tea. Early European civilisations kept their water safe by making it lightly alcoholic - Early Asian civilizations just boiled their water to make tea.

chansiky 5y ago

To be fair, Asian flush is a terrific excuse for sobriety, and I’m glad to have it.