5 ms·

The other big challenge is from a SAR (structure-activity relationship) point of view, it's completely benign looking from just about any way you look at it. It

by kortex 3y ago

The other big challenge is from a SAR (structure-activity relationship) point of view, it's completely benign looking from just about any way you look at it. It's two peptides, and a methanol (which yes, gets converted to formaldehyde, but so does fruit pectin). There's nothing zany about its structure, it's not particularly lipophilic, no receptor bindings of note, no spicy reactive groups, no alkylators, no intercalators, no redox sites. If it doesn't look like a duck, doesn't quack, doesn't waddle, doesn't fly, doesn't hang out in ponds, and hasn't shown ducklike activity over 50 years, what are the odds it's secretly a duck?

tptacek 3y ago
I had fun reading this comment to my son (early-career biochem) pretending I was coming up with it as I went along. "Does it have any alkylators? NO."
hilbert42 3y ago
Right, I'm more worried about Sucralose with all those chlorines hanging about.
headwayoldest 3y ago
So you're telling me there's a chance? Warnings like these quickly hit the Prop 65 problem - the notices are so ubiquitous you go blind to them.
- xpe 3y ago
  These notices are ineffective to say the least. Saying “everything causes cancer” is pointless because it ignores the key questions of “how often?” and “with what severity?”
  - arthur2e5 3y ago
    The IARC lists do not answer these two questions on their own either, but with the "evidence level" groups there's at least some separation from alcohol down to aspartame. These levels are still insufficient for at-a-glance risk assessment: putting mustard gas and alcohol both at level 1 can send you into a bit of a spin until you realize what the grouping is about.
  - boxed 3y ago
    Or maybe they are extremely effective, because the purpose is for the companies who sell REAL cancer inducing chemicals to muddy the waters so they can keep doing business.
    - xpe 3y ago
      Product warning labels are indeed subject to all manners of nonscientific meddling, often with a barely disguised goal of protecting a powerful industry. History is not usually kind when evaluating these kinds of compromises made to appease powerful corporations. And now, a short conversation between two people to illustrate the rhetoric in play: Person 1: “Let the market handle that; it will innovate and adapt to customer needs!” Person 2: “Except the top three players in that industry are quite profitably killing people.” Person 1: “But how can the industry recover if we act too drastically?” Person 2: I will quote what you said just above: <<Let the market handle that; it will innovate and adapt to customer needs!>> You were just saying that the market is adaptable! It seems like you are conflating the idea of protecting bad actors with the idea of setting the conditions for a healthy market. A healthy market does not kill its consumers.
  - david-gpu 3y ago
    And if something was truly dangerous then I hope they would ban it outright rather than stick a label on it. Especially when they have been sticking those same labels everywhere.
- kortex 3y ago
  Prop 65 is especially dumb because it doesn't make producers say what the risky ingredient(s) are or how potent it is. I got some fish sauce from the Asian grocer which has a p65 warning. What is it? Are there heavy metals in the fish? Nitrites? Is it smoked and thus has trace PAH? Did they find PFAS? I have no clue, but it's goddang fish sauce and so potent I put like two drops in my stir-fry (which would itself probably warrant prop 65), so idgaf. When you put the exact same warning on food as lead-containing special solder, cadmium paints, and other very obvious "don't eat this" industrial materials, it loses all efficacy.
colordrops 3y ago
You can get cancer from not getting enough sleep. There are plenty of innocuous substances that look fine chemically but disrupt sleep. It doesn't have to be directly mutagenic to cause cancer.
- xpe 3y ago
  Common writing, even from well-regarded sources, is often unnecessarily vague wrt statistics. Claim: we would benefit by building a culture where basic probability ranges are expected and used. Idea: Serious publications could: A. Set basic guidelines for talking about probability estimates; something akin to what you see in government or business intelligence publications. For example, maps terms to ranges: “highly likely”: > 90% “likely”: 70% - 90% “somewhat likely”: 50% - 70% … B. Update their editorial standards to not allow pure vagary around probabilities and impacts. Could authors write more quantitatively? At the levels of the top 100 publications, I’d guess that 80% could, with the help of research and editing staff. Would some readers be scared off? I’d guess than 80% of a college educated audience could handle it. The rest might complain, but could level up with a little peer pressure. Would articles become more rigorous? Over time, I’d hope most would. Shift the expectations and make the vocabulary less forgiving to vaguery and fudgery, and I think the incentives point in the right direction.
  - colordrops 3y ago
    Maybe it's because I'm tired but I don't see what that has to do with what I said. Did you reply to the wrong comment?
    - xpe 3y ago
      Perhaps :) Point taken. Re-reading, it looks like I skipped a transition sentence from the comment to what I wrote. (Or maybe the parent comment got edited? Not sure.) > You can get cancer from not getting enough sleep. There are plenty of innocuous substances that look fine chemically but disrupt sleep. It doesn't have to be directly mutagenic to cause cancer. I agree with the comment as written, though it strikes me that virtually no mainstream publications use writing that clarifies or quantifies these kinds of indirect relationships. I see a lot of intellectual laziness or dumbing down. Two categorical errors happen often: (A) writing “everything is connected”. This can be true in some sense while also being useless. The more interesting framing is to ask “to what degree” and under what modeling assumptions. (B) Writing about various linkages without clarifying probability and impact dilution. The connecting idea in my head was something like this: when most publications talk about cancer they tend to lack even a basic statistical language. Backstory: Having hundreds of interactions with ChatGPT, which is trained on much mainstream writing, made this interaction pattern obvious and tiresome. Another way of saying my complaint: It feels like otherwise intelligent people hit a barrier where they start speaking vaguely. They pretend like this is the best we can do. It ideally isn’t; we have extensive scientific and statistical studies. There is no reason why we as a culture have to accept such statistical phobia as quality writing.

by kortex 3y ago

tptacek 3y ago

I had fun reading this comment to my son (early-career biochem) pretending I was coming up with it as I went along. "Does it have any alkylators? NO."

hilbert42 3y ago

Right, I'm more worried about Sucralose with all those chlorines hanging about.

headwayoldest 3y ago

So you're telling me there's a chance? Warnings like these quickly hit the Prop 65 problem - the notices are so ubiquitous you go blind to them.

xpe 3y ago
These notices are ineffective to say the least. Saying “everything causes cancer” is pointless because it ignores the key questions of “how often?” and “with what severity?”
- arthur2e5 3y ago
  The IARC lists do not answer these two questions on their own either, but with the "evidence level" groups there's at least some separation from alcohol down to aspartame. These levels are still insufficient for at-a-glance risk assessment: putting mustard gas and alcohol both at level 1 can send you into a bit of a spin until you realize what the grouping is about.
- boxed 3y ago
  Or maybe they are extremely effective, because the purpose is for the companies who sell REAL cancer inducing chemicals to muddy the waters so they can keep doing business.
  - xpe 3y ago
    Product warning labels are indeed subject to all manners of nonscientific meddling, often with a barely disguised goal of protecting a powerful industry. History is not usually kind when evaluating these kinds of compromises made to appease powerful corporations. And now, a short conversation between two people to illustrate the rhetoric in play: Person 1: “Let the market handle that; it will innovate and adapt to customer needs!” Person 2: “Except the top three players in that industry are quite profitably killing people.” Person 1: “But how can the industry recover if we act too drastically?” Person 2: I will quote what you said just above: <<Let the market handle that; it will innovate and adapt to customer needs!>> You were just saying that the market is adaptable! It seems like you are conflating the idea of protecting bad actors with the idea of setting the conditions for a healthy market. A healthy market does not kill its consumers.
- david-gpu 3y ago
  And if something was truly dangerous then I hope they would ban it outright rather than stick a label on it. Especially when they have been sticking those same labels everywhere.
kortex 3y ago
Prop 65 is especially dumb because it doesn't make producers say what the risky ingredient(s) are or how potent it is. I got some fish sauce from the Asian grocer which has a p65 warning. What is it? Are there heavy metals in the fish? Nitrites? Is it smoked and thus has trace PAH? Did they find PFAS? I have no clue, but it's goddang fish sauce and so potent I put like two drops in my stir-fry (which would itself probably warrant prop 65), so idgaf. When you put the exact same warning on food as lead-containing special solder, cadmium paints, and other very obvious "don't eat this" industrial materials, it loses all efficacy.

colordrops 3y ago

You can get cancer from not getting enough sleep. There are plenty of innocuous substances that look fine chemically but disrupt sleep. It doesn't have to be directly mutagenic to cause cancer.

xpe 3y ago
Common writing, even from well-regarded sources, is often unnecessarily vague wrt statistics. Claim: we would benefit by building a culture where basic probability ranges are expected and used. Idea: Serious publications could: A. Set basic guidelines for talking about probability estimates; something akin to what you see in government or business intelligence publications. For example, maps terms to ranges: “highly likely”: > 90% “likely”: 70% - 90% “somewhat likely”: 50% - 70% … B. Update their editorial standards to not allow pure vagary around probabilities and impacts. Could authors write more quantitatively? At the levels of the top 100 publications, I’d guess that 80% could, with the help of research and editing staff. Would some readers be scared off? I’d guess than 80% of a college educated audience could handle it. The rest might complain, but could level up with a little peer pressure. Would articles become more rigorous? Over time, I’d hope most would. Shift the expectations and make the vocabulary less forgiving to vaguery and fudgery, and I think the incentives point in the right direction.
- colordrops 3y ago
  Maybe it's because I'm tired but I don't see what that has to do with what I said. Did you reply to the wrong comment?
  - xpe 3y ago
    Perhaps :) Point taken. Re-reading, it looks like I skipped a transition sentence from the comment to what I wrote. (Or maybe the parent comment got edited? Not sure.) > You can get cancer from not getting enough sleep. There are plenty of innocuous substances that look fine chemically but disrupt sleep. It doesn't have to be directly mutagenic to cause cancer. I agree with the comment as written, though it strikes me that virtually no mainstream publications use writing that clarifies or quantifies these kinds of indirect relationships. I see a lot of intellectual laziness or dumbing down. Two categorical errors happen often: (A) writing “everything is connected”. This can be true in some sense while also being useless. The more interesting framing is to ask “to what degree” and under what modeling assumptions. (B) Writing about various linkages without clarifying probability and impact dilution. The connecting idea in my head was something like this: when most publications talk about cancer they tend to lack even a basic statistical language. Backstory: Having hundreds of interactions with ChatGPT, which is trained on much mainstream writing, made this interaction pattern obvious and tiresome. Another way of saying my complaint: It feels like otherwise intelligent people hit a barrier where they start speaking vaguely. They pretend like this is the best we can do. It ideally isn’t; we have extensive scientific and statistical studies. There is no reason why we as a culture have to accept such statistical phobia as quality writing.