6177c40f

> (my submission on "offensive horticulture" did not even make honorable mention haha)

Do you have this posted anywhere? I for one would like to learn more about "offensive horticulture."

I don't understand what you're arguing. It seems like you're saying you'd rather have a city where cops and concerned citizens stop to ask if you're confused than a dense, walkable city? I also don't understand how you got that dense, walkable cities would be someplace "where passersby ignore you wantonly".

I'm not trying to discourage the use of these drugs. In fact, I would absolutely use them if I required them- their potential benefits outweigh the risks. But I also must admit that I would still feel more than a bit nervous about it.

I also should point out that "long term effects of taking them are not well understood" isn't my personal opinion per se, it's something I've read in the literature about these drugs, including relatively recent research (I wish I had a good source that summarizes this point, but I don't have one on hand). Concern about long term effects is real and legitimate, and pre-dates concern about COVID-19 vaccines (another instance where I believe the benefit far outweighs the risk, for the record). There must always be a balance between spending time testing vs. getting a pharmaceutical deployed. It would be absurd to imply that we're not making a tradeoff here.

I think that the benefit of the medication is clear, or else why would anyone take it? I definitely do not want to imply that I don't think the cost-benefit analysis comes out in favor of taking the medication. I just wanted to underscore how difficult of a situation it is to have a disease that necessitates the use of these drugs.

Not supposed to be used long term, but sometimes they are, I personally know two people who are on corticosteroids long term because nothing else works. You're right though, it's all a calculated risk because untreated disease can be life threatening, in addition to being debilitating.

All of them increase risk of cancer (EDIT: upon further review, maybe not all of them? Or maybe just with combination therapy?) and severe infection. Many of the biologics are also quite new, and the long term effects of taking them are not well understood. Plus, in some cases they don't work well enough alone and so multiple drugs are required (a biologic in combination with something like methotrexate or azathioprine is typical), which further increases risks. Anecdotally, I know of a couple people who had bizarre and severe immune reactions to biologics that left doctors baffled, so that's something that can also occur, apparently.

Also some people are just prescribed steroids like prednisone for whatever reason, which has some pretty negative long term effects.

Probably not a huge issue as long as you only eat it every so often. But I wonder about the possibility of producing varieties of pawpaw (or soursop or other related Annonas) that don't produce annonacin. Probably could be done with genetic engineering, or much more slowly with selective breeding.

Given that there are places where people consume Annonas very often, and that this may lead to alarmingly high rates of parkinsonism [1], this could be considered an effective public health intervention.

[1] https://pubmed.ncbi.nlm.nih.gov/10440304/

Should also be noted that in 2016 the trivalent OPV was replaced with a bivalent vaccine in an attempt to further mitigate the risk [1]:

> Until 2015, over 90% of cVDPV cases were due to the type 2 component in OPV. With the transmission of wild poliovirus type 2 already successfully interrupted since 1999, in April 2016 a switch was implemented from trivalent OPV to bivalent OPV in routine immunization programmes. The removal of the type 2 component of OPV is associated with significant public health benefits, including a reduction of the risk of cases of cVDPV2.

[1] https://www.who.int/news-room/questions-and-answers/item/pol...

I think the tradeoff is worth it, viruses are far more likely to do us harm than to help us out. Besides, we're entering the age when we can direct our own evolution.

This is bizarre, so they just didn't open the door to his room for over thirty years? How did they deal with the smell of a decomposing corpse?

One thing I've learned studying biology is that, while there are many decent anologies to computers, biology is really operating on a very different paradigm to the sort of programming most of us are used to.

Biology is based on "primitives" like feedback loops. For example, there are many cases where a protein that gets produced at the end of a signaling chain then goes on to stop or otherwise downregulate its own production (a negative feedback loop, positive feedback loops also exist).

Another fact that biology relies on is that increasing concentration of some molecule is essentially equivalent to increasing probability of some reaction occuring. In a negative feedback loop, for example, as the concentration of the end product increases, the probability of the reaction that that product takes part in that inhibits its own production increases. Systems then evolve such that the maximum amount of inhibition is most likely to occur when the end product is at just the right concentration.

I've often thought about making a programming language that simulates this paradigm to some extent; a probabilistic programming language where logic was implemented as feedback loops.

I think you'll find some of the tricks that (mostly) viruses use to be interesting. Take a look at ribosomal frameshifting [1], where the viral RNA has a special structure such that at a certain point during translation in the ribosome it will skip back 1 nucleotide (a -1 frameshift; -2 and +1 frameshifts have been observed as well, more rarely), thus changing the whole reading frame.

Viruses use this to encode multiple protein products in a single strand of RNA, a sort of compression. But that's not all. Say that the amount of "0-frame" protein to "-1-frame" protein needs to be at a ratio of 20:1; then if the frameshift occurs with a probability of about 5% (i.e. 5% of the time that the viral RNA is translated), these protein products will then be produced in just the right ratio (this isn't a made up example either, see [2]). So not only does this trick allow for the RNA to be compressed, it also regulates protein expression. All with just one strand of RNA.

[1] https://en.wikipedia.org/wiki/Ribosomal_frameshift

[2] https://en.wikipedia.org/wiki/HIV_ribosomal_frameshift_signa...

> So by your argument, there's no point in maintaining privacy for either piece of information (DNA / passwords).

The problem with privacy is that it's fragile. When your info is leaked, you should assume it's out there for good.

I also think that while right now when you do the cost/benefit analysis of having your DNA sequenced, you think the cost outweights the benefit. Clearly my personal calculus is different than yours, and that's ok. But I would caution you that in the future that calculation may be different for you.

So I think people will either lose privacy, or voluntarily give up some privacy for some benefit. In either case, we will need something other than privacy to protect ourselves. I think that well-enforced legislation, legislation that limits the way genetic info can be used and gives the individual more control over their own info, is really the only thing that can help.

I really don't see how this changes the threat model. If anything, I'm less worried about someone on the other side of the globe.

> Can you give an example?

See my other comment, but in short I essentially mean the true realization of "precision medicine" and gaining a greater understanding of how different genotypes result in disease, information which can be used guide treatment and to develop better treatments.

> That assumes there's someone out to get you specifically.

Not entirely true- the ability to reconstruct genotypes from environmental samples gets better all the time. I'd imagine that even with current technology, a sufficiently motivated organization could sample various locations to reconstruct the genomes of people who often visit there. With enough info, they could start building webs of genetic relation. From there, all they'd need is access to a database of samples from known individuals (which, as we can see, already exists), can chances are they could quickly deanonymize future samples. The only thing that could stop such mass collection is proper regulation.

> That's like saying there's no point in having 2FA or strong passwords, because the FSB, the FBI and Mossad can get in anyway.

Unlike your password, your DNA is unencrypted and gets spread everywhere.

> What benefit will there be?

Knowing your genetic information is currently of limited value for the majority of people, this I admit. I believe that in the future, however, the promise of precision medicine will be realized, and that having one's genetic information readily available will be crucial to receiving the best treatment possible for many diseases.

For example, take Crohn's Disease (and other inflammatory diseases more generally). The current thinking is that it is highly influenced by genetics, and that a number of different genotypes exist that can result in the phenotype we refer to as Crohn's Disease. It's conceivable that having a better understanding of someone's specific genotype could lead to more precise treatment of their condition.

> And why do you assume that it won't be accompanied by negatives?

I explicitly don't assume this, I said that the benefits will outweigh the drawbacks.

> the sole agent of evil in this world is people.

This is a specious argument. By that same measure, the sole agent of good in the world is also people. But that's irrelevant. Tech can be used both to harm and to benefit, and I'm arguing that personal gene sequencing can and will be used to provide more benefit than harm.

No, I don't think that that's obvious. At least in the US, there are already protections for genetic information (including but not limited to GINA [1]).

In the long run, I think keeping your genetic information private will be untenable- the potential benefits will outweigh the drawbacks. Plus, anyone sufficiently motivated could get your DNA somehow, you shed your DNA everywhere you go, no getting around that.

So what's left is to urge your representatives to maintain and strengthen regulations on how that information can be used, and in the long run we'll just have to trust that that will be enough.

[1] https://en.wikipedia.org/wiki/Genetic_Information_Nondiscrim...

Given that Sickle Cell Disease only affects ~20 million people in the entire world [1], and beta-thalassemia affects even fewer (maybe ~200,000 people) [2], and that this treatment currently costs millions of dollars per person, I think shareholders will be just fine.

[1] https://www.nhlbi.nih.gov/health/sickle-cell-disease

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893117/

Another common parasitic plant, dodder: https://en.wikipedia.org/wiki/Cuscuta

Also, a parasitic plant (a green alga) that infects animals: https://en.wikipedia.org/wiki/Prototheca

One would think this would happen pretty often, but at least my cursory search didn't turn up many specific examples of it happening in the US. I wonder why that is?

This is bizarre, especially this bit:

"Crop milk is a holocrine secretion, unlike in mammals where milk is an exocrine secretion."

In which Holocrine secretions are "[..] produced in the cytoplasm of the cell and released by the rupture of the plasma membrane, which destroys the cell and results in the secretion of the product into the lumen."[1]

[1] https://en.wikipedia.org/wiki/Holocrine

Something I wonder about is whether anti-malarials would work against Prototheca as well, given that some have herbicidal properties. My cursory search for whether they've been tried turns up nothing, which is unsurprising given the rarity of the disease.

Plenty of stuff. For example, Mercury, which was used as an ointment and a laxative, among other uses. Here's a surprisingly readable excerpt from a medical text written in 1787: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545546/

A bunch of random thoughts:

Why would being able to write different emails help? Wouldn't they just reuse the same email over and over again, maybe just changing the addressee's name?

Also, now I wonder what the typical response rate is for phishing emails? Are they already getting too many responses to keep up with or are they already managing just fine without bots?

I think LLMs might be better for scams carried out over instant messaging services like Discord because that probably requires greater attention and flexibility on the part of the scammer.

Still, has the number of people that could conceivably be scammed over an email or instant messaging-based scam increased? That is, will LLMs, by virtue of their response quality, responsiveness, or some other salient quality, increased the pool of people who could fall for these scams? If the answer is no, then I don't see how increased scale and throughput for human-quality text generation will really matter much.

Well you know how confusing datetime stuff can be, it's best to not be too certain.

While I don't really have an opinion either way on whether we're likely alone or not, I just want to point out that the blindspot in this argument is that all those things are truly necessary for life.

This is like a form of the anthropic principle [1], where we think that just because those conditions appear to have been necessary for our evolution (and since Earth life is the only example of life we know), that exactly those conditions must be necessary for life elsewhere.

[1] https://en.wikipedia.org/wiki/Anthropic_principle

Honestly this is the outcome I'd hope for. Got to leave some mysteries intact.

I'm a big fan of niche museums. Here's a couple neat ones from my home state (MN) that aren't on this site:

The Bakken Museum: https://thebakken.org/

Pavek Museum: https://www.pavekmuseum.org/

I've resolved that I just don't want to be advertised to. I will never stop blocking ads no matter what, even without the security benefits.

Actually given the number points my "contrarian" comments tend to get, I've come to believe my opinions are actually pretty in-line with those of the average HN user. For better or worse.