A few weeks ago, I had an absolutely delicious stout at a brew pub in Alexandria. I’m going to have to remember it, because it may have been the last time I let alcohol pass these lips. Why? Because I’m slowly turning into one of those snooty teetotalers who tut-tut over every tiny sin. It started with vegetarianism, now it’s giving up alcohol, where will it end? Refusing caffeine, turning down the enticements of naked women, refusing to dance? The bluenose in me is emerging as I get older. I shall become a withered, juiceless old Puritan with no joy left in me.
It didn’t help that last week I was lecturing on alcohol teratogenesis in my eco devo course, and it was reminding me of what a pernicious, sneaky molecule it is. I’ve known a lot of this stuff for years, but there’s a kind of blindness brought on by familiarity that led me to dismiss many of the problems. You know the phenomenon: “it won’t affect me, I only drink in moderation” and other excuses. Yeah, no. There are known mechanisms for how alcohol affects you, besides the obvious ones of inebriation.
- It induces cell death.
- It affects neural crest cell migration.
- It downregulates sonic hedgehog, essential for midline differentiation.
- It downregulates Sox5 and Ngn1, genes responsible for neuron growth and maturation.
- It weakens L1-modulated cell adhesion.
I already knew all about those first four — I’ve done experiments in zebrafish like these done in mice.
Take a normal, healthy embryo like the one in A, expose it to alcohol, and stain the brain for cell death with any of a number of indicator dyes, like Nile Blue sulfate in this example B (I’ve used acridine orange, it works the same way). That brain is speckled with dead cells, killed by alcohol. If you do it just right, you can also see selective cell death in neural crest cell populations, so you’re specifically killing cells involved in the formation of the face and the neurons that innervate it. In C, you can see the rescuing effects of superoxide dismutase, a free radical scavenger, and that tells you that one of the mechanisms behind the cell death is the cell-killing consequences of free radicals. I could get a similar reduction in the effects with megadoses of vitamin C, but that doesn’t mean a big glass of orange juice will save you from your whisky bender.
I was routinely generating one-eyed jawless fish, a consequence of the double-whammy of knocking out sonic hedgehog and cell death in the cells that make branchial arches.
You can wave away these results by pointing out those huge concentrations of alcohol we use to get those observable effects, but we only do that because we don’t have the proper sensitivity to detect subtle variations in the faces of mice or fish. So we crank up the dosage to get a big, undeniable effect.
I only just learned about the L1 effects, and that’s a case where we have a sensitive assay for alcohol’s effects. L1 is a cell surface adhesion molecule — it helps appropriate populations of cells stick together in the nervous system. It also facilitates neurite growth. It’s good for happy growing brains.
It also makes for a relatively easy and quantitative assay. Put neuronal progenitors that express L1 in a dish, and they clump together, as they should in normal development. Add a little alcohol to the medium, and they become less sticky, and the clumps disperse.
What’s troubling about this is the dosage. Adhesion is significantly reduced at concentration of 7mM, which is what the human blood alcohol level reaches after a single drink. The fetal brain may not be forming as robustly when Mom does a little social drinking that doesn’t leave her impaired at all, not even a slight buzz.
Maybe you console yourself by telling yourself a little bit does no harm, your liver soaks up most of the damage (and livers are self-repairing!), that it’s only binge drinkers who have to worry about fetal alcohol syndrome, etc., etc., etc. We have lots of excuses handy. Humans are actually surprisingly sensitive to environmental insults, we have mechanisms to compensate, but there’s no denying that we’re modifying our biochemistry and physiology in subtle ways by exposure to simple molecules.
Now maybe you also tell yourself that you’re a grown-up, I’m talking about fetal tissues, and you also don’t intend to get pregnant in the near future or ever. I’m also a great big fully adult person who is definitely not ever going to get pregnant, but development is a life-long process, and we’re all fragile creatures who nonetheless soak up all kinds of interesting and dangerous chemicals during our existence. We know alcohol will kill adult brain cells, but what else does it do? Do you want to be a guinea pig? I think that, as I age, I am becoming increasingly aware of all the bad stuff I did to myself in my heedless youth, and am starting to think that maybe I need to be a little more careful, belatedly.
Oh, you want some reassuring information? Next week we’re discussing endocrine disruptors in my class — DDT, DES, BPA, PCB, etc. — all these wonderful products of plastics and petrochemical technology. You’re soaking in them right now. They never go away. How’s your sperm count looking? Any weird glandular dysplasias? Ethanol looks pretty good compared to chlorinated and brominated biphenyls.
I drink and smoke, therefore I am. Cheers.
I have known for some time that alcohol increases the risk for cancer and I assume many others who work in the health sector also know it.
Yet I doubt many internalise this knowledge when they go out for a dinner, or go out to dance.
I suspect our brains are just not wired to process low-frequency event risks
(I am somewhat protected by being the most boring human in the world- alcohol or tobacco just do not appeal to me).
Couldn’t agree more. Just weed for me from now on.
I stopped drinking alcohol some years ago. Went through a difficult time with my depressions and drinking always made me feel worse when I felt down.
Started thinking I actually feel alright sober, so I stuck with not drinking. So it’s more about how I feel, but I’ll take the health bonus too!
That I’m now as old as may father was when the alcohol finally killed him might also be a factor.
Marijuana? Cannabinoids have been shown to impair testis function and neuronal differentiation in rats. Fortunately, studies of chronic cannabinoid use are in their early stages, so we may discover far more serious concerns, given time.
Sorry.
Oh, and now that Germany is about to legalize weed, there’s a lot of talk from concerned (conservative) politicians and headlines about the danger of THC to tennager’s brains: If you are accompanied by your parents, you can legally drink alcohol at 14 here, and buy it yourself from 16…
The fear extinction benefits of cannabinoids are current pragmatically useful and I’m not breeding anyway. It’ll be awesome when we can get society into a shape where it’s not so attractive an option.
Same for nicotine and attention. Those individual attention differences aren’t just going to adapt themselves to modern living.
I’m not giving away my weed to rats, so that’s not really relevant.
A few weeks ago, PZ posted a chart showing the relative toxicity of a bunch of different compounds. Ethanol was actually TWICE as toxic as gasoline! I don’t drink gas, I don’t drink paint thinner, and I don’t drink alcohol. I put all of those in the same category.
Well, there is also the argument that you want your life to be worth living. The end result is the same anyways.
You drank a delicious stout and still want to give up alcohol? What sort of anhedonist are you?
When most of the choices at the supermarket are crappy domestics and IPAs (still???), giving up alcohol is much easier. I do it every once in a while. Haven’t had any beer yet today…
Coffee (and sometimes tea) is the one thing I cannot do without, but usually confine my drinking of that through the morning if I want to sleep.
I am told the substance known as ecstasy is relatively safe, but you should beware of getting dehydrated.
The polynesian drink cava seems OK, as long it is not produced from the wrong part of the plant. Unlike alcohol it does not make people aggressive.
The Yemenite chewed plant substance khat ruins the teeth as it is chewed and causes excess salive. But it may not have other big disadvantages. The problem is there us no legal distribution of ut in tablet form, so tablets clsimed to be khat may be mixed up with anything. It is the same with ecstacy BTW.
Too much coffee is hard on the stomach so I supplement it with caffeinated non-sugary energy drinks. Apart from that, I have not heard anything damning about coffee, no matter what the mormons think
@birgerjohansson:
Too much of it is bad for you. Chronic high coffee can cause a lot of different shit as far as I know.
lotharloo @15
It can cause a lot of it but fairly homogeneous in character. Oh wait that’s more from the fiber instead.
As an entirely non-drinking, non-smoking, non-drug-taking killjoy with no friends, my drug of choice is smug self-righteousness. Have there been studies on the harmful effects of that recently?
Also chicken.Should I stop injecting that?
Smug self-righteousness is isn’t likely to be a problem unless misapplied. That results in stress. I’ve had reason to consider the relationship between stress and cortisol as tourette syndrome includes higher and lower peaks in the daily rhythm, but lifespan isn’t appreciably different. Intensity and stress and different is what I think is going on.
I drink cold water. So refreshing!
I’m with the Cliff Claven philosophy on alcohol and how it makes you smarter.
I’ve seen a few octogenarian patients who drink alcohol, but never any who smoke. I’ve never met a nonagenarian who drinks alcohol.
Sonic hedgehog? Really?
https://en.wikipedia.org/wiki/Sonic_the_Hedgehog
Used to play that!
@21. Wharrrrrrgarbl : Anecdata but I work – help with gardening most weeks – for an octogenarian who has just resumed smoking.
StevoR @23: Wharr whatsis is also offering anecdata. If your goal is to reach 80, or 90, or 100, then stats say avoid smoking, drinking, sweets, too much salt, crossing the road without looking both ways, being poor, living in Gaza, and a whole bunch of other risk factors.
I’ll probably die a decade or more before I might have if I didn’t indulge myself. I’m fairly sure I’ll be fine with that on my deathbed, but you never know.
It used to be that I’d only have a drink once or twice a year and never to inebriation. Then Trump got elected. Then I started drinking heavily and a lot. I needed something to numb me from the horrors I was witnessing on a daily basis.
Then, in 2022 I discovered my right kidney was cancerous. Scared me right back into teetotaling. ,
@22
I was wondering about that, too. Then I found this:
https://en.wikipedia.org/wiki/Sonic_hedgehog_protein
I’m pretty sure alcohol has differentiated many people’s midlines….
Heard from my doc today with annual checkup results. Liver enzymes elevated, and he recommended I cut back on my already relatively low alcohol consumption (three or four drinks a week) for the next three months to see if that changes the levels. So I will need to find other tasty sipping drinks to replace them.
I’ve got some sort of hereditary liver disorder. When it was first discovered, my doctor said my liver function results were what she normally sees in people with severe alcoholism. I’ve never had more than a single sip in my entire life as I can’t stand the taste or smell of alcohol, regardless of format.
Thankfully, with medication it’s doing a lot better.
I’m sure that PZ is right, one should live a strictly abstemious yet diligent life for optimal lifespan.
(https://en.wikipedia.org/wiki/Straight_edge)
I’ve tried drinking alcohol, I just don’t like it so that helps. The silliest thing people would say is that “it’s an acquired taste” which I never understood. If I don’t like the taste of something, and it isn’t good for me, why would I keep imbibing until I do like it?
I’m far more concerned about the effects of election commercials; it’s arguable that they’re in part responsible for climate change. They’re certainly responsible for a lot of headaches. And heartburn.
@26. wrog : Thanks for that.
@24. Rob Grigjanis :
True. Stas and medical advice are right of course. Science.
Same here. I wish and try to live a good life in both senses of that word – ethical and pleasurable. I do enjoy a few beers every now and then tho’ a lot less than I used to. Quality of life over mere quantity of it anyday as far as I’m concerned.
I think Socrates nailed it when he apparently said “All things in moderation including moderation.”
Thinking that Socrates said that is as dumb as confusing sonic hedgehog with Sonic the Hedgehog and needing someone else to give you the correct link.
https://quoteinvestigator.com/2022/05/13/moderation/
Not understanding things is not a virtue.
https://en.wikipedia.org/wiki/Acquired_taste
I love the cope from all the drinkers here. X-D
“Oh but anything can kill you and I’d rather a happy short life than a long unhappy life and so it’s fine for me to ingest a poison I had to force myself to like initially and which I almost certainly would be much happier doing without”.
I say this as a drinker btw. I’ve had some practice runs at stopping for six months or so but like PZ I think it’s time to put it to bed. I found to my astonishment I could actually have an even better time sober than drinking.
It’s just the pathetic cope that makes me laugh. Rationalization is a thing us humans do.
@ 34 Jim Balter
The former was literally named after the latter and guess what results you get if you Google “sonic hedgehog”. There’s nothing “dumb” about people not being aware of an obscure technical term. Knock of the stupid arrogance Jim, you come off as a total wanker.
So, if we give up all the pleasurable vices and hew unto miserable virtues we shall live forever? No? Though not. So what’s the point?
Or you can fuck all the way off because pretending to not understand how people commonly use terms doesn’t make you smarter, better, or more interesting.
Also… https://www.oxfordreference.com/display/10.1093/oi/authority.20110803095347932 or https://dictionary.cambridge.org/dictionary/english/acquired-taste
Aaaaalllll the way off, please.
Not to take anything away from PZ, but I first heard about sonic hedgehog about a decade ago on Neil Shubin’s program Your Inner Fish.
Also, there was at least one supercentanarian — in this case reaching the age of 112 — who smoke and drink his entire adult life.
Coffee. Coffee…
Is a pot and a half a day a problem?
Tooth twitches, eyeball migrates to chin
My grandfather used to let me drink his coffee. I got hooked early. I have had to cut it down some due to anxiety getting generalized. Maybe I’m better with the sensations now. I’m not the kind of person who can drink it before bed though.
Silentbob @36 Tabby Lavalamp @38
That’s Balter’s thing, swooping in periodically to eviscerate people. Maybe has some connection to solar flares or lunar cycles. I dunno.
Hemi et al: Maybe he came home drunk and the thread about alcohol set him off…?
Raging Bee @43
He started off ok in @19 but much later on a switch in his head changed his demeanor.
From 4:03 pm to 1:05 am is plenty of time to get drunk. And this isn’t the first time he’s had a late-night meltdown either.
“With mirth and laughter let old wrinkles come. And let my liver rather heat with wine than my heart cool with mortifying groans.”
Shakespeare: MofV.
My medical doctor said to me the last time I visited that there is a relatively new metastudy that is about long term studies of ethanol consumption. There is no safe amount of alcohol. There is no benefit to alcohol. Studies that have shown it to be good in moderation have been refuted.
seachange @47:
OK.
Define ‘benefit’. I’m happier drinking moderately than I was not drinking for several years.
Long term studies indicate there’s no benefit to [insert any activity which could lead to harm or death].
@Silentbob #35,
I don’t think it’s a cope if you moderate your use and genuinely don’t have a problem.
I’m an addict, so I can’t do that. Alcohol’s not my problem, but it makes me more likely to use other stuff that is a problem, so I don’t drink. But not everyone needs to be in recovery, IMO.
@Rob Grigjanis #48
Most alcoholics consider themselves moderate drinkers.
@47– Those studies purporting that small amounts of alcohol had health benefits were pretty dodgy in the first place. Lots marginal statistical differences in posthoc analysis implying at best trivial benefits, amplified by industry PR, and reported uncritically by journalists who should not be writing about health or science.
Happens all the time. Happened with chocolate. Happened with palm oil. Even happened with cigarettes in the 2000s! There is a small cottage industry in the health sciences of undertaking poorly-designed research in the hope of finding some trivial, probably statistically anomalous health benefit for substances linked to cashed-up industry groups.
i was introduced to alcohol at a young age and it became a problem in my teenage and early adult years. i wasn’t a hardcore alcoholic, but i was drinking to excess at least twice a week. i still have problems with self-control around alcohol when it’s flowing freely, but i don’t buy it to keep in the house anymore.
@34. Jim Balter : Well, forgive me for reading something once (or twice or thrice or however many times), loving the quote and then repeating it and believing the attribution given for it. A heinous sin to be sure.
Thanks for the link with extra info on its source. Seriously, thankyou, something new learnt.
As for me being grateful to others and thanking them for an informative link that I didn’t “need” but did appreciate with some good info that made my life – and probly others lives too – easier, well, nasty bllghter ain’t chya?
You be you. As for me? I’m reminded of the old joke that being vegan doesn’t make you live longer. It just makes it seem like it.
flange #50
Most “alcoholics” are moderate drinkers.