Too much serendipity

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.

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?

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.

> 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.

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.

Aren't there hundreds of compounds in an orange?

I do agree with the conclusion though, we likely have tasted (or could have tasted) weaker options over the years.

I wonder if the real conclusion is "we don't understand the human body enough to predict what will work so getting lucky is our only option".

I looked at some of the sources linked on Wikipedia for the other anecdotes.

Ace-K: Newton, D. E. (2007). Food Chemistry (New Chemistry). Available on libgen. Also describes the other serendipitous discovery stories, but with no citation or evidence. For Ace-K, there are conflicting accounts of whether the chemist was licking his fingers to pick up a piece of paper or rubbing out a white spot on his sweater or shirt.

Sucralose: Eurekas and Euphorias: The Oxford Book of Scientific Anecdotes. Available on libgen. Also describes the same anecdotes for other drugs. The only supporting evidence for any of them is is a direct quote from James Schlatter on the discovery of aspartame:

"I was heating the aspartame in a flask with methanol when the mixture bumped [boiled abruptly] onto the outside of the flask. As a result some of the powder got onto my fingers. At a slightly later stage, when licking my fingers to pick up a piece of paper, I noticed a very strong, sweet taste. Initially, I thought that I must have had some sugar on my hands from earlier in the day. However, I quickly realised this could not be so, since I had washed my hands in the meantime. I therefore traced the powder on my hands back to the container into which I had placed the crystallised aspartylphenylalanine methyl ester. I felt that this dipeptide ester was not likely to be toxic and I therefore tasted a little of it and found that it was the substance which I had previously tasted on my finger."

The book chalks up the 'test'/'taste' mixup with Ace-K to a language barrier (Phadnis's first name was Shashikant).

Processed Foods and the Consumer claims that Schlatter licked his finger to 'provide friction before reaching for a thin piece of laboratory equipment.'

The story about the discovery of saccharin is from The 100 Most Important Chemical Compounds: A Reference Guide, which also does not cite a source for the story.

An American Chemical Society Molecule of the Week article also reports the "tasting his hand after dinner" story for the discovery of saccharin, but notes that "in another version of the story" he tasted it on his cigarette, just like in the cyclamate discovery story. Of course, the NY Times obit for Sveda, discoverer of cyclamates, is that "he brushed his lips without having washed his hands and found that his fingers tasted sweet," rather than that he put his cigarette into the chemical.

I am asking this question genuinely because I have been told that I am unable to "read between the lines" and that I am considered "transactional" in nature where I need things spelled out for me. I don't necessarily agree with this assessment... could it be that I'm not capable of extracting the content "between the lines?"

but please don't ask about what exactly they're cooking too much, keep the discussion on the how they are cooking it hahahha