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▲IgE disruptor for food allergy with Claude-enabled antibody design [pdf] (divergencelabs.com)
ValleZ 9 hours ago [-]
Opus 5.5 blocks any biology research that even remotely looks like this. I guess that the "safeguards" are for peasants only.
jenders 7 hours ago [-]
This
JumpCrisscross 14 hours ago [-]
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.

bflesch 11 hours ago [-]
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).
JumpCrisscross 10 hours ago [-]
> 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.

Madmallard 6 hours ago [-]
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.
JumpCrisscross 5 hours ago [-]
> 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.

Madmallard 56 minutes ago [-]
> 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.

manmal 14 hours ago [-]
How can IgE get bored? That doesn’t sound right. Why would the body, a master of efficiency, produce IgE just for fun?
JumpCrisscross 13 hours ago [-]
> 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/

changoplatanero 14 hours ago [-]
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.
adam791 14 hours ago [-]
Hygiene hypothesis
dzhiurgis 11 hours ago [-]
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.
trollbridge 10 hours ago [-]
Majority of people here in USA I know have some kind of allergy, including people of EE / Slavic descent.
dzhiurgis 9 hours ago [-]
I mean grown up in EE. Literally know nobody with allergies.

So must be environment that they are brought up in?

polishdude20 13 hours ago [-]
So... Let's bring back the worms I guess?
JumpCrisscross 11 hours ago [-]
> 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...

modeless 8 hours ago [-]
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.
Melatonic 1 hours ago [-]
Examples ?
nezi 12 hours ago [-]
The worms can cause issues. I'd rather no worms.
jaykru 12 hours ago [-]
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.
nextaccountic 11 hours ago [-]
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

masfuerte 9 hours ago [-]
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.
trollbridge 10 hours ago [-]
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.

nextaccountic 7 hours ago [-]
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

adrianN 6 hours ago [-]
Pinworms are mostly harmless and trivially treated.
bflesch 11 hours ago [-]
More likely the worms just get shredded and are part of the food now
altairprime 14 hours ago [-]
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.
jrflo 13 hours ago [-]
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...
altairprime 13 hours ago [-]
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!
jrflo 11 hours ago [-]
Ah sorry, the divergence blog called it a preprint: https://divergencelabs.com/?p=publications
hcknwscommenter 9 hours ago [-]
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/
ChrisArchitect 12 hours ago [-]
Related:

Early progress on accelerating drug development with Claude

https://news.ycombinator.com/item?id=50265609

areoform 11 hours ago [-]
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.
    > 
    > Details: [bio]
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.

rfgplk 11 hours ago [-]
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.

dboreham 7 hours ago [-]
Thanks. Always wanted to know what the secret Styrofoam material in US thermonuclear weapons was...
areoform 4 hours ago [-]
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

emscb 7 hours ago [-]
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