[HN Gopher] Too much serendipity
       ___________________________________________________________________
        
       Too much serendipity
        
       Author : HR01
       Score  : 146 points
       Date   : 2024-01-22 17:26 UTC (5 hours ago)
        
 (HTM) web link (www.lesswrong.com)
 (TXT) w3m dump (www.lesswrong.com)
        
       | RcouF1uZ4gsC wrote:
       | > Look at sucrose and aspartame side by side:
       | 
       | > Molecular structures of sucrose and aspartame, looking very
       | different I can't imagine someone looking at these two molecules
       | and thinking "surely they taste the same".
       | 
       | They don't taste the same. Aspartame has a very nasty aftertaste
       | as compared to sucrose.
        
         | imglorp wrote:
         | Yes, to my taste, all the sweeteners have an aftertaste and an
         | odor including stevia.
        
           | cgh wrote:
           | Re stevia, apparently how you taste it is determined by how
           | sensitive your bitter taste receptors happen to be. It's
           | somehow also related to why some people can't stand cilantro,
           | for example.
           | 
           | For me, stevia is simply sweet with no aftertaste so I guess
           | I'm lucky in this regard.
        
             | wccrawford wrote:
             | Stevia? My wife has much stronger bitter receptors than
             | most people (including me, and I thought mine were strong)
             | but Stevia is fine for her.
             | 
             | Aspartame, though, she absolutely despises.
             | 
             | I think they're both fine, but I can pick up a hint of what
             | she dislikes from Aspartame.
             | 
             | Sucralose is also fine for both of us.
        
             | bityard wrote:
             | You are! As one who identifies as keto, I have experience
             | with a wide range of artificial sweeteners. Stevia is one
             | of my favorites but I can definitely taste the bitterness.
             | Which is why I only use it either in combination with other
             | sweeteners (e.g. Erythritol), or in places where only a
             | slight amount of sweetness is desired.
             | 
             | Edit: I just had a thought: are we talking about putting it
             | in coffee here? Because the bitterness of coffee and the
             | bitterness of Stevia are pretty close and I can see the
             | former masking the latter easily.
        
               | fellowniusmonk wrote:
               | Monk Fruit/Stevia liquid sweeteners (sans erythritol) are
               | my go to for coffee and any slightly bitter food for this
               | very reason.
        
         | johnchristopher wrote:
         | I wonder if people have different genetic predispositions that
         | influences how sugar taste to them. Like I have with cilantro
         | (a bit, a tiny tiny bit is okayish but more than that and
         | it's.. ugh... it's not even soap it's.. bleh..).
        
       | FergusArgyll wrote:
       | I loved the writing but I don't get the point or the title. Am I
       | supposed to infer some sort of conspiracy theory? or is it just
       | supposed to be funny?
        
         | ElevenLathe wrote:
         | I don't think it's meant to imply a conspiracy, rather that lab
         | safety around novel compounds is probably not as tight as
         | people assume it is.
         | 
         | I will put forth another (possible) explanation: fake sugar has
         | to be widely marketed, and "we were doing Important Science
         | when we accidentally discovered this fake sugar" is a more
         | marketable, easy-to-understand story than "we added/removed
         | groups on a range of compounds determined likely to be sweet
         | based on a literature review, in order of how amenable the
         | reactions are to mass production, then tested each of them in
         | rats".
        
         | cmyr wrote:
         | I don't think there's some huge point beyond exploring an
         | interesting question, and raising it in a forum where it's
         | possible some people with more specific domain knowledge might
         | offer some insight.
        
         | cubefox wrote:
         | I think the author suggests that chemical-psychological
         | research is quite inefficient, given that so many discoveries
         | were random discoveries rather than products of systematic
         | search and invention.
        
         | empath-nirvana wrote:
         | The point is that chemists are tasting a lot of the novel stuff
         | they synthesize, if it doesn't look like it's going to cause
         | instant cancer, even they they aren't supposed to.
         | 
         | Watching NileRed regularly, it does not at all surprise me.
        
       | WhatsTheBigIdea wrote:
       | What a fabulous analysis! The serendipity is remarkably high!
       | 
       | I suppose penicillin might be a good addition to the list of
       | powerful compounds discovered by happenstance?
       | 
       | Does this mean that innovation is basically a brute force
       | calculation? Humans simply trying permutations until something
       | hits?
        
         | vacuity wrote:
         | Considering how we all seem to be the product of millions of
         | years of hit-or-miss natural selection, it feels almost natural
         | that our advancements have also had a great deal of
         | luck/improbability.
        
           | hinkley wrote:
           | Some homebrewers will wax nostalgic about how the human sense
           | of smell/taste can detect almost all of the ways that
           | fermentation can go wrong and make it toxic.
           | 
           | But we also keep pushing back earliest dates for precursors
           | to civilization, I start to wonder if maybe there aren't
           | graveyards of people who couldn't distinguish thymol from
           | ethanol and selected themselves out of human history via
           | acute liver failure.
        
             | sudosysgen wrote:
             | Animals do eat fermented food, through fallen/rotting
             | fruits, so perhaps the thymol sensitivity predates
             | hominids.
        
               | thfuran wrote:
               | Yeah, the ability to detect toxins likely to appear in
               | the food supply seems evolutionarily important.
        
             | kfarr wrote:
             | Yeah exactly this is not just random, it's "guided search"
             | as commented by a sibling
        
         | ninjaK4t wrote:
         | I mean history suggests that's the case. Took centuries for
         | Copernicus to exist.
         | 
         | AI has been an idea for decades. It wasn't until transformers
         | in the last few years we had big gains.
         | 
         | Google and giant institutions focus on fiat revenue stability
         | over the long term, in line with political ideology. Few big
         | ideas come out of that. I think what Adam Smith is said to have
         | written applies; division of labor taken to the extreme will
         | result in humans dumber than the lowest animal.
         | 
         | We iterated on our current political system over the Boomers
         | lives. Next generations are tired of the threat of brute force
         | from the elders who the kids now see as in no position to back
         | up those threats given their age. They're abandoning norms of
         | the last 30-40 years, which IMO, is enabled by abandonment of
         | thousands of years of obligation to preserve religion.
         | 
         | There are shorter iterative periods too; 15 years ago comic
         | movies went crazy with Iron Man, iPhone blew up; now we're
         | iterating on AI generated content and spatial headsets. 15
         | years prior (with some wiggle room for margin of error)
         | "information super highway" was coming.
         | 
         | On the shorter scales there seems to a pattern of 3-5 year
         | warmup and 7-10 year plateau, with a cooldown of 2-3 years as
         | the masses lose interest. This aligns with neuroscience
         | experiments that show our brains devalue old patterns after
         | roughly 15 years.
         | 
         | Generational churn and lack of generalized sense of obligation
         | to the past (via abandonment of religious buy in by westerners)
         | could free the future to live in cycles that align with
         | scientific measurement versus obligation to be parrots that
         | recite past memes.
        
           | aeneasmackenzie wrote:
           | Copernicus is a bad example. He proposed a heliocentric
           | system based on vibes. Actual progress required decades of
           | cutting-edge precision measurements by Brahe and then
           | analysis by Kepler. Objections to heliocentrism were on
           | scientific grounds which were resolved by the discovery of
           | inertia, Airy disks, and stellar aberration.
        
         | hinkley wrote:
         | How did we ever figure out that aspens and willows have aspirin
         | analogs in their bark? Boredom? Starvation food?
         | 
         | Psychedelic mushrooms make sense. You see it, you eat it.
         | Willow bark tea is a whole process.
        
           | doubled112 wrote:
           | Makes you wonder about tobacco.
           | 
           | Hey, all the bugs that are eating that plant are dying. Let's
           | see what happens if we smoke it.
        
             | neuromanser wrote:
             | More like: This plant has no insect parasites, it must be
             | special somehow, let's try and use it in different,
             | increasingly "close approach" ways. I mean, humans must
             | have figured quite early that on average, inhaling smoke of
             | a poisonous plant has a fraction of the effect of chewing
             | the same. Someone gets really sick after chewing some
             | leaves, their family burns the rest of the "crop" and they
             | get high.
        
           | throwaway4aday wrote:
           | Back in the day people made tea out of anything they could
           | get their hands on that wasn't outright poisonous.
           | https://en.wikipedia.org/wiki/Herbal_tea#Varieties
           | 
           | Also, if you're in constant pain you'll try all kinds of
           | random stuff to make the pain go away. If necessity is the
           | mother of invention then desperation is its father.
        
         | BriggyDwiggs42 wrote:
         | It's much smarter than random, more like a guided search.
        
       | elevatedastalt wrote:
       | I think it feels serendipitous only if you think of "sweet" taste
       | (or for that matter any taste) as occurring in this giant
       | continuum of tastes where hitting a specific spot on that
       | continuum is probabilistically impossible.
       | 
       | Ultimately, we experience tastes thanks to chemical receptors on
       | the tongue, and as long as a substance triggers those receptors
       | we experience a certain taste.
       | 
       | Now of course if triggering needs a very very specific
       | combination of atoms, then it is not very probable, but we know
       | especially from drug research that you can use similarities in
       | molecular structure or sometimes in say the electron cloud of the
       | molecule to perform this triggering. Caffeine for eg is a
       | selective adenosine antagonist that fools the body and binds to
       | adenosine receptors. Now of course int the case of caffeine the
       | structures are somewhat similar, but you could imagine similar
       | stuff happening with other molecules too
       | 
       | If you think of it as that sort of problem, it's not that
       | surprising that many different types of molecules might achieve
       | the same effect.
        
         | hinkley wrote:
         | That artificial sweetener they mention halfway through, the one
         | that gorillas are evolving not to taste, man that amused me
         | when I first heard about it a few years ago. Chalk one up for
         | hominidae.
        
         | BurningFrog wrote:
         | > * it's not that surprising that many different types of
         | molecules might achieve the same effect*
         | 
         | But the point of the post is that only five molecules found by
         | dumb luck have had a useful sweetening effect.
        
       | amelius wrote:
       | Unfortunately, the chemists merely tasted, not ingested.
       | Otherwise they would have known that their newly found artificial
       | sweeteners cause nasty bowel issues.
        
       | ysofunny wrote:
       | or you know, consider how many people have gotten into chemistry
       | because they wanna learn how to cook, or simply to cook better.
       | 
       | but please don't ask about what exactly they're cooking too much,
       | keep the discussion on the how they are cooking it hahahha
        
       | perfectritone wrote:
       | I'm left curious as to why our taste receptors are so attuned to
       | sweetness if high sugar foods weren't historically correlated
       | with being high in energy.
        
         | lemax wrote:
         | Perhaps because the high sugar foods that occur in nature
         | contain nutrients we don't get elsewhere and help us fight
         | disease. These sugars are also naturally packaged in a way that
         | makes them behave quite unlike added sugars, they don't lead to
         | the same insulin spikes or high blood pressure, and consuming
         | fruits like berries alongside more processed, artificially
         | sweetened foods can even reduce the insulin spikes of those
         | foods.
         | 
         | https://nutritionfacts.org/blog/what-about-all-the-sugar-in-...
        
         | gpsx wrote:
         | I have thoughts about that, but IANAN (nutritionalist). Not all
         | energy is the same, as in fructose (in sucrose, which we sense
         | as sweeter) versus glucose (what composes carbs, and also in
         | sucrose), two simple sugars. Glucose goes more directly into
         | the bloodsteam during digestion. Fructose does not go straight
         | to the bloodstream but is processed by the liver. Although it
         | gets into the bloodstream slower, it gets stored by the liver
         | faster, and we use this as an energey resevoir when we are not
         | getting energy directly thorugh digestion. So maybe we crave
         | this somtimes when we need to rebuild our energy stores. Or at
         | least it seems that way for me. I crave sugar/fruit sometimes,
         | particularly after exercising. I don't generally even eat
         | sweets/desserts, so my body apparently isn't fooled into always
         | wanting sugar. I would guess from my experience sugar plays a
         | specific role and I want it at a certain time and not others.
         | 
         | Incidently, I get a headache when I eat processed sugar, but
         | not fruit. (However, fruit will also give me a headache if I
         | carmelize it, cooking it at a high temperature for a long
         | time.) Anyway that is one reason I avoid sweetened foods and
         | maybe why I don't get sucked into eating sugar all the time.
         | And people think I am trying to be super healthy...
        
         | paulpauper wrote:
         | They are high in energy. carbs used by muscles for energy first
         | over protein and fat
        
         | Sesse__ wrote:
         | If nothing else: It's certainly useful that mother's milk
         | tastes good to babies. Imagine what an evolutionary
         | disadvantage it would be if it tasted bitter.
        
         | koromak wrote:
         | 1) Its still very, very high in energy. We're built to use it.
         | 2) Fruits contain all sorts of good vitamins and minerals along
         | with sugar. Two birds with one stone. 3) I don't know if we are
         | any less "attuned" to it than fat or protein. Most people would
         | eat a good steak over a bag of candy.
        
       | Imnimo wrote:
       | Are compounds that might be seen in a clinical trial drawn from
       | the same distribution as compounds that a lab chemist might
       | accidentally taste? Is it weird that there's no overlap of a
       | compound that is both very sweet and medically active?
        
       | cubefox wrote:
       | This poses the opposite question: What might we have missed?
       | Maybe there are some reverse-accidents, some significant random
       | discoveries that, due to their randomness, didn't happen.
        
         | GolfPopper wrote:
         | There was an SF story I read years ago where the core concept
         | was that humanity had somehow "missed" an obvious power-
         | source/FTL drive, which meant that the "solution" to the Drake
         | Equation is that the galaxy is full of intelligent, star-
         | spanning empires that are effectively stuck at a late-1800s
         | tech level (with starships), because getting to there was easy,
         | and doing all the complex 20th century stuff humanity has done
         | is _really hard_. Hijinks and hilarity ensues when they reach
         | earth.
        
           | wheybags wrote:
           | Do you remember what it was called?
        
             | caffeinated_me wrote:
             | I believe they're referring to the short story of The Road
             | Not Taken, by Turtledove.
             | 
             | https://en.wikipedia.org/wiki/The_Road_Not_Taken_(short_sto
             | r...
             | 
             | PDF of story: https://www.eyeofmidas.com/scifi/Turtledove_R
             | oadNotTaken.pdf
        
           | ptx wrote:
           | Is it "The Road Not Taken" by Harry Turtledove? The Wikipedia
           | description seems to match. (If so, ChatGPT got it on the
           | second attempt.)
        
       | johngossman wrote:
       | I recently learned that anesthesia is the same. Not only has no
       | anesthesia ever been developed except through "serendipity." Not
       | only that, but anesthesia that works for humans also effect a
       | wide range of things including plants and bacteria. But why is an
       | active area of research. There are even speculations that there
       | may be quantum effects involved. Biology and chemistry are
       | insanely complex.
        
         | thfuran wrote:
         | How do you determine whether a plant or bacterium is
         | anesthetized?
        
           | boston_clone wrote:
           | I'm really just reposting one of the first few DDG links
           | after inputting your question, but this article covers a few
           | different plants:
           | 
           | https://www.acsh.org/news/2017/12/11/general-anesthesia-
           | work...
        
           | reaperman wrote:
           | I don't think they measure if plants/bacterium are
           | anesthetized, but in exposing them to things that cause
           | anesthesia in humans, other potentially unrelated effects are
           | noticed.
           | 
           | Many compounds/mechanisms, especially hormones and
           | neurotransmitters, are widely "re-used" across different
           | biologies for completely different things. They're
           | essentially generic semaphores, and the action caused by
           | raising the semaphore can be basically anything. There's a
           | lot of variance in effect even among different instances of
           | human species, often quite unpredictable, contradictory, and
           | profound.
           | 
           | It's sort of like "hey we already have this testosterone
           | thing, it's currently used to call [function A] but we could
           | refactor that to use it to initiate [function B] instead"
           | (testosterone causes growth in many mammals but inhibits
           | growth in lizards, so female lizards are larger than male
           | lizards)
           | 
           | or "hey we already have the genes to make serotonin for
           | gastrointestinal regulation, but it's not used for anything
           | in the brain. The blood-brain-barrier already prevents
           | somatic serotonin from reaching the brain so we could have a
           | completely different function for it in the brain and
           | regulate gut and brain serotonin in isolation of eachother"
           | 
           | or "hey we have this cholesterol thing that we've been using
           | as a signaling hormone ever since we were on version Plant,
           | maybe we could write a factory that modifies the cholesterol
           | we eat and use it to produce new semaphores like estrogen and
           | testosterone to support a more complex messaging system and
           | handle all the new effects rather than overloading the
           | existing semaphore".
           | 
           | Edit: Probably slightly better to think of them as the
           | coefficients for activation functions, but nothing here is
           | meant to be anywhere remotely close to a direct analogy.
           | Taking any of this literally would be a misreading.
        
         | jdewerd wrote:
         | > there may be quantum effects involved
         | 
         | Quantum Mechanics is why atoms and molecules exist and form
         | bonds. QM is the physics of chemistry. Without QM, chemistry
         | does not happen. The universe would just be a big churning mess
         | of particles and you would never get little lego pieces that
         | snap together according to repeatable rules that, when
         | repeated, form macroscopic substances of innumerable
         | description up to and including life itself.
         | 
         | So QM is no doubt involved, but on this scale it is either a
         | trivial fact or an indication that someone tried to lean on a
         | classical approximation, it broke, and they had to revise it
         | (which arguably says more about the approximation than it says
         | about the underlying behavior).
         | 
         | Apologies for the nitpick. It's a pet peeve of mine that
         | discussions of QM tend to focus so hard on the strange behavior
         | that they forget to mention where QM fits into the bigger
         | picture and leave people with the impression that it only
         | matters under special circumstances when in fact it matters so
         | much that you can hardly have "matter" without it.
         | 
         | ------------
         | 
         | Re: anesthetic, a large fraction of simple halocarbon compounds
         | have intense neural effects, so anyone doing halocarbon
         | chemistry would quickly be put on the "scent" even if they
         | weren't tasting everything in the Sigma Aldrich catalog.
        
           | bordercases wrote:
           | Do you know for sure they meant only those quantum effects
           | which operate near or at the classical limit?
        
           | PakG1 wrote:
           | As a non-physicist and non-chemist who keeps running into
           | quantum mechanics only through headlines, extra thanks for
           | pointing this out. It's quite obvious in retrospect to
           | acknowledge that quantum mechanics is the physics of
           | chemistry, and I don't know why I didn't see that before. It
           | certainly helps to view a lot of things in a new light.
        
           | akoboldfrying wrote:
           | I would say everyone understands that "quantum effects"
           | refers to situations in which classical approximations break
           | down.
           | 
           | Likewise when we say "numerical issues", it's understood that
           | we're talking about situations in which the usual
           | approximation of real numbers by floating point
           | representations breaks down. "Disk corruption" doesn't
           | necessarily mean anything is physically wrong with the disk,
           | only that its contents have become inconsistent with the
           | filesystem abstraction it normally supports, etc.
        
           | ddellacosta wrote:
           | (In support of your point about QM:)
           | 
           | To contrast with an example of where quantum mechanics is
           | relevant at the level of biology--this is one I'm familiar
           | with:
           | 
           | https://www.sciencenews.org/article/quantum-fragility-may-
           | he...
           | 
           | Unfortunately I'm not finding anything related to anesthesia
           | except for hand-wavy pieces about "quantum consciousness"
           | (anyone, please do correct me with a link or two if I'm
           | wrong). I blame Sir Roger Penrose, if only because him
           | talking speculatively about it (even in a sophisticated,
           | informed way) seems to give so many others leeway to speak
           | far more casually about the same topic, with far less
           | coherence. This is why we can't have our cake and eat it too
           | I guess
        
             | johngossman wrote:
             | More discussion in "Life on the Edge: The Coming of Age of
             | Quantum Biology." I can't recommend the book unreservedly,
             | but it's worth checking out reviews.
        
               | ddellacosta wrote:
               | Will take a look--thanks. Also, re: anesthesia,
               | appreciate that you linked to the "Electron spin
               | changes..." paper in the other comment, will check it
               | out!
        
           | johngossman wrote:
           | I understand your frustration, sorry for the poor wording.
           | 
           | "Electron spin changes during general anesthesia in
           | Drosophila" https://pubmed.ncbi.nlm.nih.gov/25114249/
           | 
           | I learned about this from Nick Lane's book "Transformer: The
           | Deep Chemistry of Life and Death"
        
         | Ductapemaster wrote:
         | There's a fascinating Radiolab episode about anesthesia that is
         | worth a listen: https://radiolab.org/podcast/anesthesia
        
       | stcredzero wrote:
       | _I can't imagine someone looking at these two molecules and
       | thinking "surely they taste the same"._
       | 
       | I think that's more of a shortcoming of our method of diagramming
       | molecules. It might be more apparent if we had 3D visualizations
       | of the molecules and the receptors.
        
       | imzadi wrote:
       | What I learned from this is never eat at a pot luck full of
       | chemists.
        
       | GolfPopper wrote:
       | Sucralose and aspartame are both reliable migraine triggers for
       | me, and have been at least since my early 20s. Stevia and
       | monkfruit are fine. The only other even semi-consistent migraine
       | trigger for me is alcohol.
       | 
       | I've successfully avoided migraines for years by carefully
       | avoiding sucralose and aspartame (and drinking little to no
       | alcohol), but even a small serving of something "sugar-free" and
       | within a few hours I'll get a crippling migraine. In college, I
       | spent a while testing, and the link between both sucralose and
       | aspartame and my migraines was perfectly reliable.
       | 
       | Alcohol in general has been harder to nail down. A single beer
       | won't normally trigger a migraine, while sometimes a single glass
       | of wine or small cocktail will. If I drank to excess it was hard
       | to tell the difference between a hangover and a migraine; I
       | wasn't that invested in social alcohol consumption, so I've
       | mostly just been a teetotaler since college. Absinthe uniquely
       | reliably gives me an acephalgic migraine with aura around 12
       | hours after drinking.
       | 
       | Edited to add: I've just stayed away from ace-K and sugar-
       | alcohols as a precaution. I'm past the point in my life where I
       | have any real interest in risking crippling migraines for the
       | sake of personal curiosity.
        
       | kirse wrote:
       | I think this is because all newly-discovered knowledge inherently
       | reflects the miracle of new life. The point at which an "unknown-
       | unknown" piece of information is birthed into our awareness and
       | becomes a known fact is always going to be a fascinating and
       | surprising story. The excitement of informational peek-a-boo, the
       | pulling back of the universal curtains on a discovery we never
       | expected - we might be a little older, but the reaction never
       | changes. Entrepreneurs call it their business pivot, chemists
       | call it serendipity.
        
       | joneholland wrote:
       | This "I did my own research" pseudoscience has no reason to be on
       | hackernews.
        
         | mcherm wrote:
         | Really? Because I think Hacker News often features posts by
         | hackers and amateurs trying to tackle something normally
         | handled by professionals.
         | 
         | The comments would be a great place to reply with references to
         | the ACTUAL research on how often chemists taste the chemicals
         | they are working with.
        
       | Damogran6 wrote:
       | Loctite Blue may or may not taste sweet. I'm not reproducing the
       | experiment.
        
         | Cthulhu_ wrote:
         | Didn't lead taste sweet as well?
        
           | FreeFull wrote:
           | Lead(II) acetate specifically is sweet.
        
       | phkahler wrote:
       | The amino acid Glycine is sweet and it's good for you. Not really
       | patentable though.
        
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