Hacker News: MontyCarloHall

European commission adds exemptions to portable battery removability rules

MontyCarloHall — Fri, 17 Jul 2026 17:18:15 +0000

Article URL: https://environment.ec.europa.eu/news/commission-adds-exemptions-portable-battery-removal-rules-2026-07-14_en

Comments URL: https://news.ycombinator.com/item?id=48949800

Points: 2

# Comments: 0

New comment by MontyCarloHall in "Elevated error rate across multiple models"

MontyCarloHall — Tue, 23 Jun 2026 15:25:14 +0000

Right. If this were truly a pure scaling issue, I’d expect the interface would offer an archive.is-esque “Claude is at capacity; your prompt is #XXX/YYY in the queue; estimated time remaining: ZZZ seconds”

Instead, the whole system just shits the bed, catastrophically.

New comment by MontyCarloHall in "Elevated error rate across multiple models"

MontyCarloHall — Tue, 23 Jun 2026 15:16:47 +0000

Another data point: GitHub is extremely insistent its employees maximally use AI for internal development [0], and we’ve concomitantly seen its reliability fall off a cliff in the last year or so.

[0] https://github.com/resources/insights/ai-powered-workforce-p...

New comment by MontyCarloHall in "Elevated error rate across multiple models"

MontyCarloHall — Tue, 23 Jun 2026 14:57:07 +0000

   I don’t prompt Claude anymore. I have loops running that prompt Claude and figuring out what to do. My job is to write loops.
   — Boris Cherny, head of Claude Code

Reliability is a direct reflection of the quality of the underlying infrastructural code. If even Anthropic, the company with the world's best agentic vibecoders, has horribly unreliable infrastructure, it really says something about the quality of the world's best agentically produced code.

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Mon, 15 Jun 2026 15:39:52 +0000

Including additional guides is negligible with respect to the overall LNP capacity, which can contain a few thousand nucleotides. The CRISPR/Cas mRNA is about 5 kilobases total, and each guide is on the order of 100 bases.

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Sun, 14 Jun 2026 02:36:54 +0000

Sure, but my point is that convergent selective pressure across different individuals' tumors is strong enough that they independently arrive on the same resistance mechanisms to a given therapy, e.g. [0]. Just like if you performed the same bacterial antibiotic resistance experiment [1] across multiple independent trials, you'd repeatedly get the same result.

[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC2538882/

[1] https://news.ycombinator.com/item?id=48505231#48507925

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Sat, 13 Jun 2026 16:17:40 +0000

In practice, you’d use multiple guides targeting multiple mutations, so that the probability of having/acquiring multiple resistance mutations abrogating every guide from binding would be infinitesimal.

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Fri, 12 Jun 2026 21:43:03 +0000

Even with 100% delivery efficacy, editing efficacy is nowhere near 100%. CRISPR/Cas editors will reliably detect the target sequence but will not reliably edit it in order to repair the mutant allele, whereas CRISPR/Cas12a2 will activate and destroy chromatin ~100% of the time when it detects the target.

As is often the case, it's a lot easier to indiscriminately destroy than precisely (re)build.

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Fri, 12 Jun 2026 21:21:14 +0000

Agreed. Assuming it's ultimately proven to work in vivo, I think the endgame of this therapy is multiple guides targeting multiple mutations along with multiple delivery mechanisms (a formulation-diverse cocktail of LNPs + eVLPs [0]?). Sure, tech like [0] is futuristic and fanciful, but so is the tech of the OP, and both will probably reach in vivo maturity around the same time.

[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC8809250/

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Fri, 12 Jun 2026 18:50:38 +0000

>Depending on how the LNPs are designed, would resistance also potentially cripple the cancer cells?

Yes, if the LNP could be engineered to target an essential surface receptor, which is still a very tough problem. It would also not solve the issue of the payload successfully entering the cell but being subsequently degraded.

>I've heard about drug resistance in bacteria leading to slower growth / reduced virulence. Maybe the same would occur with cancers. A drug that could effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.

This is essentially how treatment for chronic lymphocytic leukemia happens (hence why it's called "chronic"). People with CLL can stay on BTK inhibitors for decades, often until they die of other natural causes.

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Fri, 12 Jun 2026 18:46:28 +0000

>there's no "be a better/stronger cancer and spread more effectively to more hosts"

No, but there is "be a better/stronger cancer cell and don't succumb to whatever therapy is killing its neighboring cells." It's exactly akin to how dosing isolated populations of bacteria with antibiotics selects for individual cells that are resistant, which then multiply and dominate [0], just like a tumor.

[0] https://www.youtube.com/watch?v=plVk4NVIUh8

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Fri, 12 Jun 2026 18:44:16 +0000

This would shorten the timeframe for cells to mutate and acquire resistance mechanisms, but would not address the issue of cells with preexisting (epi)genetic resistance mechanisms that would then be promptly selected for.

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Fri, 12 Jun 2026 18:40:48 +0000

Nonetheless, we see the exact same resistance mechanisms to the same therapies recur across individuals, e.g. [0]. Convergent evolution is a harsh mistress.

[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC2538882/

New comment by MontyCarloHall in "CRISPR tech selectively shreds cancer cells, including "undruggable" cancers"

MontyCarloHall — Fri, 12 Jun 2026 18:26:58 +0000

The idea of using CRISPR/Cas to detect tumor-specific mutations that aren't necessarily oncogenic and then kill the cell is not a new one [0, 1, 2]. However, previous studies used Cas9, which just damages the DNA at the target site; this uses Cas12a2, which is far more destructive because it shreds the chromatin in the cell once activated by detecting the target sequence.

As with any cancer treatment, it's likely the tumor will evolve resistance. My guess is that cells will find ways to reject the lipid nanoparticles used to deliver the CRISPR/Cas mRNA and associated guide sequence(s), either via modifications to the cell surface (preventing LNP uptake) or via changes to endosomal/lysosomal pathways (causing the mRNA payload to get degraded before it has a chance to be translated into protein).

[0] https://pubmed.ncbi.nlm.nih.gov/28575452/

[1] https://www.nature.com/articles/s41598-018-30205-2

[2] https://www.nature.com/articles/s41467-020-18875-x

New comment by MontyCarloHall in "India's surprise baby bust"

MontyCarloHall — Fri, 05 Jun 2026 18:44:33 +0000

>[B]y far the most common reason given is that the cost of living has risen to such an extent that they feel that rearing children has become unaffordable.

That's certainly a factor, though very aggressive financial incentives for parents don't seem to work very well [0, 1, 2]. Not to mention that in rich countries, educational attainment and income are negatively correlated with fertility [3]. My theory there is that people's high-powered careers provide them more self-satisfaction than having kids.

>it's the fact that they can't even afford to buy somewhere to live.

It's funny you mention this. Some friends said they weren't having a second kid because they couldn't afford a three bedroom house, not realizing that kids sharing bedrooms was the norm for middle class families until very recently. Having one bedroom per kid was a luxury just 30-40 years ago.

>I won't comment on your assertion that the freedom to watch "adult-appropriate movies on a big TV in the living room" is a more fulfilling state of being than parenthood

It's not my assertion, it's something a couple deciding to not have another kid literally told me. They missed being able to have substantial amounts of adult time, and were actively counting down the days until their only child was old enough to amuse himself for long periods of time. Having another kid would reset that clock.

[0] https://www.economist.com/europe/2026/03/19/viktor-orbans-pr...

[1] https://www.theguardian.com/world/2024/feb/28/south-korea-fe...

[2] https://worldcrunch.com/culture-society/boosting-birth-rates...

[3] https://www.oecd.org/en/publications/society-at-a-glance-202...

New comment by MontyCarloHall in "India's surprise baby bust"

MontyCarloHall — Fri, 05 Jun 2026 16:48:30 +0000

As I wrote in another reply, I meant “hedonism” in its non-colloquial, neutral sense, i.e. the pursuit of individual pleasure and happiness above all else, which was a mistake on my part. My general point is that all the activities I listed (which only become abundantly available in rich, industrialized societies) yield more individual pleasure than having children.

New comment by MontyCarloHall in "India's surprise baby bust"

MontyCarloHall — Fri, 05 Jun 2026 16:31:07 +0000

Agreed with everything you wrote. I meant “hedonism” in its non-colloquial, neutral sense, i.e. the pursuit of individual pleasure and happiness above all else, which judging by the other replies was a mistake on my part.

>But having children is not intrinsically non-hedonistic. It's just one of many self-fulfilling activities we choose from

Exactly, and my point is that all the activities I listed (which only become abundantly available in rich, industrialized societies) are more self-fulfilling than having children.

New comment by MontyCarloHall in "India's surprise baby bust"

MontyCarloHall — Fri, 05 Jun 2026 16:28:43 +0000

I never made any value judgment on whether it’s bad or good. “Hedonism” is simply the focus of individual pleasure and happiness above all else, and everything I listed is an example of things that lead to individual happiness that are antithetical to having many children.

New comment by MontyCarloHall in "India's surprise baby bust"

MontyCarloHall — Fri, 05 Jun 2026 15:42:19 +0000

I'd call it hedonism if a couple wants to be able to go out on a date on a whim, easily take a vacation, watch adult-appropriate movies on a big TV in the living room, maintain good sleep/health habits, keep a flexible schedule unconstrained by school pickups/staying home with a sick kid, etc.

These are all real examples of why people I know delayed having kids, curtailed the number they had, or never had them altogether.

New comment by MontyCarloHall in "India's surprise baby bust"

MontyCarloHall — Fri, 05 Jun 2026 15:30:49 +0000

This has happened to every single society [*] as it industrializes [0], and offering extensive support and incentives to parents (e.g. as has been tried in Scandinavian countries) does very little to reverse this trend [1, 2].

My hypothesis is that as societies industrialize, they afford their population more and more activities that are simply more fun and rewarding than having children. So many people I know put off having children (or curtailed the number they had) because they were reluctant to give up the activities only available in a childfree/one-and-done life. Ultimately, we are hedonistic creatures, and having kids is antithetical to the myriad hedonic pursuits available in wealthy, industrialized societies.

[*] Israel is the lone exception, due to its Orthodox Jewish population.

[0] https://ourworldindata.org/global-decline-fertility-rate

[1] https://pub.nordregio.org/r-2024-13-state-of-the-nordic-regi...

[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC10049131/