The Nonlinear Library LW - There is way too much serendipity by Malmesbury
Jan 19, 2024
11:15
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: There is way too much serendipity, published by Malmesbury on January 19, 2024 on LessWrong.
Crossposted from substack.
As we all know, sugar is sweet and so are the $30B in yearly revenue from the artificial sweetener industry.
Four billion years of evolution endowed our brains with a simple, straightforward mechanism to make sure we occasionally get an energy refuel so we can continue the foraging a little longer, and of course we are completely ignoring the instructions and spend billions on fake fuel that doesn't actually grant any energy. A classic case of the Human Alignment Problem.
If we're going to break our conditioning anyway, where do we start? How do you even come up with a new artificial sweetener? I've been wondering about this, because it's not obvious to me how you would figure out what is sweet and what is not.
Look at sucrose and aspartame side by side:
I can't imagine someone looking at these two molecules and thinking "surely they taste the same". Most sweeteners were discovered in the 20th century, before high-throughput screening was available. So how did they proceed?
Let's look into these molecules' origin stories.
Aspartame was discovered accidentally by a chemist researching a completely unrelated topic. At some point, he licked his finger to grab a piece of paper and noticed a strong sweet taste.
Cyclamate was discovered by a grad student who put his cigarette on his bench, then smoked it again and noticed the cigarette was sweet.
(I know what you're thinking. The kind of guy who lights up cigarettes in a chemistry lab and places them in the middle of uncharacterised compounds before taking them to his mouth again, must have died young of an interesting death. I checked - he proceeded to live to the old age of 87.)
Saccharine was discovered by a researcher who ate bread without washing his hands and noticed the bread was sweet.
Acesulfame K was also discovered serendipitously by a chemist licking his fingers, although the legends don't specify the exact circumstances behind the finger-licking.
There's an exception: sucralose was actually the fruit of rational, deliberate design. The researchers reasoned that, if you do slight modifications to sucrose, you could find a molecule that is no longer metabolized but still activates the sweetness receptors. So they started from the formula for sucrose, then made carefully-designed chemical modifications to the structure until
Haha, just kidding:
While researching novel uses of sucrose and its synthetic derivatives, Phadnis was told to "test" a chlorinated sugar compound. According to an anecdotal account, Phadnis thought Hough asked him to "taste" it, so he did and found the compound to be exceptionally sweet.
It is therefore a fact of the world that virtually all the popular synthetic sweeteners were discovered accidentally by chemists randomly eating their research topic.[1]
I think this is a suspiciously high amount of serendipity. I see two options:
Super-sweet molecules like aspartame are commonplace - there are plenty of molecules hundreds of times sweeter than sucrose, but we only know the few that were ingested by accident,
Super-sweet molecules are very rare, it's just that chemists accidentally taste a lot of chemicals. Entire chemistry departments routinely taste the entire space of possible molecules, but they don't notice unless the molecule has a strong taste.
To get an idea of how often chemists taste the chemicals they are working with, let's consider how often a molecule taken at random will taste sweet. That's equivalent to asking: how specific are our sweet taste receptors?
Low-hanging fruits
Why do we have sweet receptors in the first place?
I thought that we craved sugars so much because of their energy content - if we eat plants that contain a lot of sugars, we can break the...
Crossposted from substack.
As we all know, sugar is sweet and so are the $30B in yearly revenue from the artificial sweetener industry.
Four billion years of evolution endowed our brains with a simple, straightforward mechanism to make sure we occasionally get an energy refuel so we can continue the foraging a little longer, and of course we are completely ignoring the instructions and spend billions on fake fuel that doesn't actually grant any energy. A classic case of the Human Alignment Problem.
If we're going to break our conditioning anyway, where do we start? How do you even come up with a new artificial sweetener? I've been wondering about this, because it's not obvious to me how you would figure out what is sweet and what is not.
Look at sucrose and aspartame side by side:
I can't imagine someone looking at these two molecules and thinking "surely they taste the same". Most sweeteners were discovered in the 20th century, before high-throughput screening was available. So how did they proceed?
Let's look into these molecules' origin stories.
Aspartame was discovered accidentally by a chemist researching a completely unrelated topic. At some point, he licked his finger to grab a piece of paper and noticed a strong sweet taste.
Cyclamate was discovered by a grad student who put his cigarette on his bench, then smoked it again and noticed the cigarette was sweet.
(I know what you're thinking. The kind of guy who lights up cigarettes in a chemistry lab and places them in the middle of uncharacterised compounds before taking them to his mouth again, must have died young of an interesting death. I checked - he proceeded to live to the old age of 87.)
Saccharine was discovered by a researcher who ate bread without washing his hands and noticed the bread was sweet.
Acesulfame K was also discovered serendipitously by a chemist licking his fingers, although the legends don't specify the exact circumstances behind the finger-licking.
There's an exception: sucralose was actually the fruit of rational, deliberate design. The researchers reasoned that, if you do slight modifications to sucrose, you could find a molecule that is no longer metabolized but still activates the sweetness receptors. So they started from the formula for sucrose, then made carefully-designed chemical modifications to the structure until
Haha, just kidding:
While researching novel uses of sucrose and its synthetic derivatives, Phadnis was told to "test" a chlorinated sugar compound. According to an anecdotal account, Phadnis thought Hough asked him to "taste" it, so he did and found the compound to be exceptionally sweet.
It is therefore a fact of the world that virtually all the popular synthetic sweeteners were discovered accidentally by chemists randomly eating their research topic.[1]
I think this is a suspiciously high amount of serendipity. I see two options:
Super-sweet molecules like aspartame are commonplace - there are plenty of molecules hundreds of times sweeter than sucrose, but we only know the few that were ingested by accident,
Super-sweet molecules are very rare, it's just that chemists accidentally taste a lot of chemicals. Entire chemistry departments routinely taste the entire space of possible molecules, but they don't notice unless the molecule has a strong taste.
To get an idea of how often chemists taste the chemicals they are working with, let's consider how often a molecule taken at random will taste sweet. That's equivalent to asking: how specific are our sweet taste receptors?
Low-hanging fruits
Why do we have sweet receptors in the first place?
I thought that we craved sugars so much because of their energy content - if we eat plants that contain a lot of sugars, we can break the...