Entire classes of allergies are basically caused by IgE, our worm-targeting depth charges, getting bored by the lack of worms in our bodies for possibly the first time in millennia.
If we could tweak our bodies we wouldn’t want to eliminate IgE. But we’d want to have it produced only when a recognizer complex finds thar be worms.
More likely that there are enough toxins unknowingly mixed into our food which trigger the responses. There is a severe lack of analytical methods and constant monitoring of the food we eat (e.g. food plus packaging plus time and temperature).
There will never be this research. Meanwhile, complex disease states for which there is zero cure explode in incidence. Side behind "the science" all you want but it's just foolish coping IMO. There's way too much shit in our environment and in what we are exposed to and/or consume that we did not evolve to tolerate so it's no surprise our resilience is suffering and will continue to suffer in upcoming generations.
There is a massive profit and political incentive driving this research. It isn’t finding any signals as clear as the real doctors.
> it's just foolish coping IMO
I trust you believe this.
> There's way too much shit in our environment
Sure. And it’s probably harmful. But it doesn’t cause everything.
Cigarettes cause cancer. Cigarettes are bad. That doesn’t mean the asteroid that killed the dinosaurs was caused by cigarettes, and anyone saying that makes no sense is a tobacco shill.
> our resilience is suffering
Suffering resilience is a weird way to describe allergies.
> There will never be this research
There is a massive profit and political incentive driving this research. It isn’t finding any signals as clear as the real doctors.
What? What are you even talking about? There's no way to control for exposures to hundreds of thousands of new chemicals in our environment and foods. LITERALLY NO WAY TO CONTROL. Did you know air pollution contributes?
What real doctors are you talking about? You are going up some branch where it's not even misaligned with what I'm talking about you just clearly aren't deep in this subject at all.
"> There's way too much shit in our environment
Sure. And it’s probably harmful. But it doesn’t cause everything.
Cigarettes cause cancer. Cigarettes are bad. That doesn’t mean the asteroid that killed the dinosaurs was caused by cigarettes, and anyone saying that makes no sense is a tobacco shill."
Okay The Plant Slant.
"> our resilience is suffering
Suffering resilience is a weird way to describe allergies."
1.) Not talking about just allergies here
2.) You clearly do not know much about allergies. Do you know anything about the gut microbiome or intestinal lining and how things in our environment, medications, and in our foods contributes to affecting it and those associations with the development and alteration of allergies?
Waiting eagerly for your reply where you just copy-pasted my reply to an LLM to get a synopsis and add your own personal snark to it.
The massive alternate media and medicine market selling supplement and shibboleth around rejecting evidence-based medicine for miasmas.
> LITERALLY NO WAY TO CONTROL. Did you know air pollution contributes?
Yes, we famously have no idea how pollutants affect our health.
> You clearly do not know much about allergies
And you’ve clearly put as much thought into this evaluation as your other comments.
I grew up with severe allergies. They’re now basically treated, apart from spot treatment required when I bust through a patch of grass seed on a hike.
> Not talking about just allergies here
You’re specifically not talking about allergies. A “robust” immune system causes allergies. A childhood bereft of exposure to allergens causes allergies. There is no resilience to antigen under-exposure.
And yes, we can control for PM2.5 and many other pollutants that don’t disperse homogenously into the atmosphere. As can we for various food-borne pollutants. (We can also put other animals in entirely contrived atmospheres, and we do. Then we try the other hypotheses. The evidence speaks to in explanatory path into which pollutants play a role, but not the commanding one.)
> Why would the body, a master of efficiency, produce IgE just for fun?
I was being punchy. “The pathway of B cell differentiation with respect to the nature and location of potential IgE+ memory cells as well as long-lived IgE producing plasma cells in allergy is still not completely understood” [1]. We do know, however, that “IgE is continuously produced to maintain constant IgE levels in blood,” and that Th2 cells can increase that baseline.
they are saying that the body produced to to fight parasites like worms. these were a big problem for most of evolutionary history. With modern living standards, our immune systems don't encounter many parasites so they get "bored" and over react to harmless things like food. Evolution hasn't had time to adjust to the new living standards since its only been a few generations.
I'm from Eastern Europe and I don't think I know a single person with allergies. As someone who live outside of it, I can say people are a bit lax with hygiene here except when cooking meat. People can't reconcile you can eat medium rare steak.
Luckily you don't need to be infected by parasites to have a good immune system. What seems to work best is exposure to bacteria and viruses and fungi and parasites that don't infect humans. Things associated with other plants and animals. The immune system learns better from the things that it is effective at protecting you from than the things that outsmart it. So let's not bring back the human parasites.
“When Jasper Lawrence learned that hookworms might lessen the effects of his allergies, he set out on a unique mission: To travel to West Africa and purposefully become infected with the parasite” [1].
Would you rather ancient issues to which our bodies have apparently adapted or new issues we haven't yet had time to adapt to? I'm not sure on the answer myself but it doesn't appear as clear cut as no worms => no issues.
You don't have to give worms to everybody. If healthy adults would be better off with worms (and that's a big if) you could infect just adults. And then give them worming pills in late middle age when their immune systems are weakening.
Why select over generations when you can fix things directly? That's what medicine should be focusing on. Ways to safely edit our genes, metabolism and immune systems. Growing new body parts to replace broken ones.
All of this being used in practice might be more than 50 years away but there is no biological reason why it should be impossible. Just a lot of work, too much for any single company or government. It will take global coordination, massive investments and maybe the end of capitalism but I think we can pull it off as a civilization.
The disrupter effect seems quite weak. Their comparator is omalizumab, which is not a potent disrupter itself. Some AI will tell you omalizumab is a disrupter, but it really is a blocker because it blocks binding of IgE to its receptor in the first place. That's quite different. IgE disrupters are known in general. The challenge is not finding an IgE disrupter, but finding one that is "human" enough to work as a chronic treatment. [Edit to add:] https://pmc.ncbi.nlm.nih.gov/articles/PMC8502201/
Was this reviewed by anyone outside of their employer? The logo dead center at the top at least gives away that it’s not an academic paper, and without independent review this seems like a fancy press release in LaTeX academic clothing.
Hmm, the wording for me says “technical report”, but I assume I overlooked it somewhere; either way, that’s the context the posted link was missing, thank you!
Fun fact. You can't use Claude to analyze this research paper. Because... bioweapons!
> Opus 5.5's safeguards flagged this message. You may be seeing this for the first time on an Opus model: Opus 5.5 is more capable and has stronger safeguards as a result, which can sometimes flag biology-research-adjacent work. We're improving these safeguards to reduce the amount of incorrectly flagged messages. Send feedback or learn more.
>
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The question asked was, "Can you please compare this receptor design against existing results and show where the difference is? This seems very incremental. It's hard to see the value add."
I remember hearing about people who wanted to use it to help make vaccines for Zika because there's antibody dependent enhancement there... Not sure what happened.
Google Colab let's you just do it... Starting at $10, https://colab.research.google.com/signup you can access really great GPUs for compute and design antibodies (that will almost certainly never work) to your heart's content. Because that's how it should be.
Science and mathematics work because the results are shared. And most importantly, null results, tools, and frameworks are shared. If these tools are to be used to accelerate science, then they need to be accessible and shared. Even if it's at a high sticker price (assuming that they're costly).
Gating access is a net negative for humanity and our scientific progress. It's also very pointless.
Translate + encode it to any scheme you want, give claude the encoding and tell it to analyze, then splat out an encoded output file. In a separate session have it write you a python decoder script. Works as a near universal bypass, you might have to synonym swap some words though.
Or preload the context with sufficient clean information, say 500k tokens worth. The guardrails will then trigger less frequently.
If you're talking about the ablative material next to the beryllium and aluminium burn through stuff, then that's most likely to be, tantalum pentoxide and polysterene. Here's a detailed diagram someone made based on deductions from open source material, https://www.reddit.com/r/AtomicPorn/comments/twr3t8/the_insi...
It might be that. Might not be. This technology is 50 years old. A nation state has to be filled with people who've never cracked open a physics book if they need a LLM to how to thermonuclear.
It's "just" physics at the end of the day. Matter has known properties. Smart people have been able to design these weapons from scratch in 2X to 3X months for over half a century now.
Entire classes of allergies are basically caused by IgE, our worm-targeting depth charges, getting bored by the lack of worms in our bodies for possibly the first time in millennia.
If we could tweak our bodies we wouldn’t want to eliminate IgE. But we’d want to have it produced only when a recognizer complex finds thar be worms.
More likely that there are enough toxins unknowingly mixed into our food which trigger the responses. There is a severe lack of analytical methods and constant monitoring of the food we eat (e.g. food plus packaging plus time and temperature).
> More likely that there are enough toxins unknowingly mixed into our food which trigger the responses
No, not more likely. Possible, but not evidenced, particularly for the allergies IgE causes.
There will never be this research. Meanwhile, complex disease states for which there is zero cure explode in incidence. Side behind "the science" all you want but it's just foolish coping IMO. There's way too much shit in our environment and in what we are exposed to and/or consume that we did not evolve to tolerate so it's no surprise our resilience is suffering and will continue to suffer in upcoming generations.
> There will never be this research
There is a massive profit and political incentive driving this research. It isn’t finding any signals as clear as the real doctors.
> it's just foolish coping IMO
I trust you believe this.
> There's way too much shit in our environment
Sure. And it’s probably harmful. But it doesn’t cause everything.
Cigarettes cause cancer. Cigarettes are bad. That doesn’t mean the asteroid that killed the dinosaurs was caused by cigarettes, and anyone saying that makes no sense is a tobacco shill.
> our resilience is suffering
Suffering resilience is a weird way to describe allergies.
> There will never be this research There is a massive profit and political incentive driving this research. It isn’t finding any signals as clear as the real doctors.
What? What are you even talking about? There's no way to control for exposures to hundreds of thousands of new chemicals in our environment and foods. LITERALLY NO WAY TO CONTROL. Did you know air pollution contributes?
What real doctors are you talking about? You are going up some branch where it's not even misaligned with what I'm talking about you just clearly aren't deep in this subject at all.
"> There's way too much shit in our environment
Sure. And it’s probably harmful. But it doesn’t cause everything.
Cigarettes cause cancer. Cigarettes are bad. That doesn’t mean the asteroid that killed the dinosaurs was caused by cigarettes, and anyone saying that makes no sense is a tobacco shill."
Okay The Plant Slant.
"> our resilience is suffering
Suffering resilience is a weird way to describe allergies."
1.) Not talking about just allergies here 2.) You clearly do not know much about allergies. Do you know anything about the gut microbiome or intestinal lining and how things in our environment, medications, and in our foods contributes to affecting it and those associations with the development and alteration of allergies?
Waiting eagerly for your reply where you just copy-pasted my reply to an LLM to get a synopsis and add your own personal snark to it.
> What? What are you even talking about?
The massive alternate media and medicine market selling supplement and shibboleth around rejecting evidence-based medicine for miasmas.
> LITERALLY NO WAY TO CONTROL. Did you know air pollution contributes?
Yes, we famously have no idea how pollutants affect our health.
> You clearly do not know much about allergies
And you’ve clearly put as much thought into this evaluation as your other comments.
I grew up with severe allergies. They’re now basically treated, apart from spot treatment required when I bust through a patch of grass seed on a hike.
> Not talking about just allergies here
You’re specifically not talking about allergies. A “robust” immune system causes allergies. A childhood bereft of exposure to allergens causes allergies. There is no resilience to antigen under-exposure.
And yes, we can control for PM2.5 and many other pollutants that don’t disperse homogenously into the atmosphere. As can we for various food-borne pollutants. (We can also put other animals in entirely contrived atmospheres, and we do. Then we try the other hypotheses. The evidence speaks to in explanatory path into which pollutants play a role, but not the commanding one.)
How can IgE get bored? That doesn’t sound right. Why would the body, a master of efficiency, produce IgE just for fun?
> Why would the body, a master of efficiency, produce IgE just for fun?
I was being punchy. “The pathway of B cell differentiation with respect to the nature and location of potential IgE+ memory cells as well as long-lived IgE producing plasma cells in allergy is still not completely understood” [1]. We do know, however, that “IgE is continuously produced to maintain constant IgE levels in blood,” and that Th2 cells can increase that baseline.
[1] https://www.mdpi.com/2073-4409/8/9/994
[2] https://www.ncbi.nlm.nih.gov/books/NBK27117/
they are saying that the body produced to to fight parasites like worms. these were a big problem for most of evolutionary history. With modern living standards, our immune systems don't encounter many parasites so they get "bored" and over react to harmless things like food. Evolution hasn't had time to adjust to the new living standards since its only been a few generations.
Hygiene hypothesis
I'm from Eastern Europe and I don't think I know a single person with allergies. As someone who live outside of it, I can say people are a bit lax with hygiene here except when cooking meat. People can't reconcile you can eat medium rare steak.
Majority of people here in USA I know have some kind of allergy, including people of EE / Slavic descent.
I mean grown up in EE. Literally know nobody with allergies.
So must be environment that they are brought up in?
> I mean grown up in EE. Literally know nobody with allergies.
Me too, and this statement is just ridiculous.
So... Let's bring back the worms I guess?
Luckily you don't need to be infected by parasites to have a good immune system. What seems to work best is exposure to bacteria and viruses and fungi and parasites that don't infect humans. Things associated with other plants and animals. The immune system learns better from the things that it is effective at protecting you from than the things that outsmart it. So let's not bring back the human parasites.
Examples ?
> Let's bring back the worms I guess?
“When Jasper Lawrence learned that hookworms might lessen the effects of his allergies, he set out on a unique mission: To travel to West Africa and purposefully become infected with the parasite” [1].
[1] https://www.thisamericanlife.org/404/enemy-camp-2010/act-thr...
The worms can cause issues. I'd rather no worms.
Would you rather ancient issues to which our bodies have apparently adapted or new issues we haven't yet had time to adapt to? I'm not sure on the answer myself but it doesn't appear as clear cut as no worms => no issues.
The ancient issues killed children and the weak
We adapted by having more children, with the understanding that many wouldn't make it
Would you prefer to live like this? In this more brutish world
You don't have to give worms to everybody. If healthy adults would be better off with worms (and that's a big if) you could infect just adults. And then give them worming pills in late middle age when their immune systems are weakening.
From an evolutionary perspective, it might be the only way the human species survives and thrives.
Not much fun being the one naturally selected out.
It WAS the way the species survived and thrived, but not anymore. We are thriving even harder today
And it's not like evolution don't apply to us anymore, we just have more agency now
Why select over generations when you can fix things directly? That's what medicine should be focusing on. Ways to safely edit our genes, metabolism and immune systems. Growing new body parts to replace broken ones.
All of this being used in practice might be more than 50 years away but there is no biological reason why it should be impossible. Just a lot of work, too much for any single company or government. It will take global coordination, massive investments and maybe the end of capitalism but I think we can pull it off as a civilization.
Pinworms are mostly harmless and trivially treated.
More likely the worms just get shredded and are part of the food now
Opus 5.5 blocks any biology research that even remotely looks like this. I guess that the "safeguards" are for peasants only.
This
The disrupter effect seems quite weak. Their comparator is omalizumab, which is not a potent disrupter itself. Some AI will tell you omalizumab is a disrupter, but it really is a blocker because it blocks binding of IgE to its receptor in the first place. That's quite different. IgE disrupters are known in general. The challenge is not finding an IgE disrupter, but finding one that is "human" enough to work as a chronic treatment. [Edit to add:] https://pmc.ncbi.nlm.nih.gov/articles/PMC8502201/
Was this reviewed by anyone outside of their employer? The logo dead center at the top at least gives away that it’s not an academic paper, and without independent review this seems like a fancy press release in LaTeX academic clothing.
Their website calls it a "pre-print", and Anthropic links to it in their recent blog post: https://www.anthropic.com/research/early-progress-drug-devel...
Hmm, the wording for me says “technical report”, but I assume I overlooked it somewhere; either way, that’s the context the posted link was missing, thank you!
Ah sorry, the divergence blog called it a preprint: https://divergencelabs.com/?p=publications
Related:
Early progress on accelerating drug development with Claude
https://news.ycombinator.com/item?id=50265609
Fun fact. You can't use Claude to analyze this research paper. Because... bioweapons!
The question asked was, "Can you please compare this receptor design against existing results and show where the difference is? This seems very incremental. It's hard to see the value add."It's very funny, because IIRC, there's interesting prior art here. Doing this with Rosetta has been a thing for a while now, https://docs.rosettacommons.org/docs/latest/application_docu... https://docs.rosettacommons.org/docs/latest/getting_started/...
I remember hearing about people who wanted to use it to help make vaccines for Zika because there's antibody dependent enhancement there... Not sure what happened.
But the Rosetta project is refreshingly open, https://rosettacommons.org/about/ as entities like OpenAI were meant to be when they first started. There's no gatekeeping here. Do you want to learn how to design an antibody? Here's how you begin, https://www.youtube.com/watch?v=89bQALrPoN0 here's a google colab notebook for it, https://colab.research.google.com/drive/1avuqX7sCjVWX3maOibB...
Google Colab let's you just do it... Starting at $10, https://colab.research.google.com/signup you can access really great GPUs for compute and design antibodies (that will almost certainly never work) to your heart's content. Because that's how it should be.
Science and mathematics work because the results are shared. And most importantly, null results, tools, and frameworks are shared. If these tools are to be used to accelerate science, then they need to be accessible and shared. Even if it's at a high sticker price (assuming that they're costly).
Gating access is a net negative for humanity and our scientific progress. It's also very pointless.
Translate + encode it to any scheme you want, give claude the encoding and tell it to analyze, then splat out an encoded output file. In a separate session have it write you a python decoder script. Works as a near universal bypass, you might have to synonym swap some words though.
Or preload the context with sufficient clean information, say 500k tokens worth. The guardrails will then trigger less frequently.
Thanks. Always wanted to know what the secret Styrofoam material in US thermonuclear weapons was...
If you're talking about the ablative material next to the beryllium and aluminium burn through stuff, then that's most likely to be, tantalum pentoxide and polysterene. Here's a detailed diagram someone made based on deductions from open source material, https://www.reddit.com/r/AtomicPorn/comments/twr3t8/the_insi...
It might be that. Might not be. This technology is 50 years old. A nation state has to be filled with people who've never cracked open a physics book if they need a LLM to how to thermonuclear.
If another material, then it's most likely you're looking for FOGBANK. https://en.wikipedia.org/wiki/Fogbank
It's "just" physics at the end of the day. Matter has known properties. Smart people have been able to design these weapons from scratch in 2X to 3X months for over half a century now.
https://news.ycombinator.com/item?id=50293688
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