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

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

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

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

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.

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

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

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

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...

>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.

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

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/

[0] https://woodgears.ca/eyeball/index.html

But those individuals are much bigger shareholders in the company they work for. Downsizing the office footprint of a single company has a tiny marginal effect on the overall real estate market, but can incur enormous savings for the company, and enormous personal rewards to the people making the decision to downsize and save money.

Individuals are notoriously bad at considering collective externalities. If a CFO realizes that they could save tens of millions of dollars per year on real estate by switching to remote-only, they’re not going to then think “but if everyone did this, it would hurt the commercial real estate holdings I have in my portfolio.” No, the CFO is thinking “announcing that we’re saving 8 figures per annum on real estate is going to pop the share price of my company (and thus my equity holdings), and likely net me a really fat cash bonus.” By similar logic, CTOs, who likely have considerable technology investments, would want to needlessly maximize tech spend. Instead, they get lauded for cutting IT costs.

(Dillinger is also shown running "ENCOM Linux" -- is the VFX artist a BSD user? As he cycles through his buffers, we see a split second of `hanoi-unix`; definitely not the type to pay attention during boring board meetings!)

[0] https://www.youtube.com/watch?v=y-86iKkn6k0#t=3m55

I stand somewhere in the middle: while our IP laws are far too restrictive, the folly of abolishing IP altogether has been effectively laid bare by AI companies.