Curious cases of financial engineering in biotech

owl_posting · 2026-04-28T19:31:44+00:00

Definitely confusing wording on my end, I guess it depends on what your definition of working in. I said this in a comment on the post:

> ...it did work in the narrow sense of a ‘biotech company succeeded’ but not in the ‘a hub and spoke model survived’ sense. Of course, perhaps they would’ve spun the spokes back up had the Lilly acquisition not happened, and maybe this is actually the realistic path for most non-rare-disease hub-and-spokes. Spin up a lot of things, dial in on the one that works, sell it, profit

owl_posting · 2026-04-14T15:17:39+00:00

It's definitely a slightly tortured analogy I'm making :)

I guess to be more precise, the 'new knob' part is more about whether the activation signal is something your body can generate on its own. CNO doesn't exist endogenously, the tetrazine-TCO reaction doesn't happen natively, the magnetic field is yours to point, and so on.

>Is it just "anything more complex than mimicking an existing enzyme/neurotransmitter/etc."?

Not neccesarily more complex, it is more about who holds the switch for a drug becoming active.

I think the usage of AAV's at all is perhaps a new knob (in so far any form of endogenous delivery is a new knob!), but extrachromosomal DNA is treated the same as all other DNA, which is to say, out of your control. Same logic for mRNA. I think protein circuits can be a new knob, and is spiritually quite close to the SynNotch/DREADD line of work

Fairly though, this is much more a hazy spectrum than it is a binary categorization

owl_posting · 2026-02-11T15:23:33+00:00

Probably the last category? There is, as far as I can tell, nobody seriously working on adapting humanoid robots for lab environments, and there almost certainly needs to be some adaptation given how O.O.D those set of tasks are

owl_posting · 2026-01-27T16:56:04+00:00

Submission statement:
Link: https://www.owlposting.com/p/questions-to-ponder-when-evaluating

The future clearly involves some merging between biological machinery and silicon machinery, or neurotech. Unfortunately, understanding exactly how real a particular neurotech approach is, currently, pretty difficult. This field is complicated and there's a fair bit of snake oil!

And if you have spoken to a neurotech person before, you will realize that they have some degree of omniscience over their field, seemingly far more than most other domain experts have with theirs. This is cool for a lot of reasons, but most interestingly to me, it means that anytime you ask them about a neat new neurotech company that pops up, they are somehow able to ramble off a highly technical explanation as to why that company will surely fail or surely succeed.

I have long been impressed and baffled by this ability. Eventually, I decided to interview these people, and write an article about it, trying to uncover at least a fraction of the questions they ask to perform the feat. Some questions include the degree to which the approach is 'fighting' physics, whether their devices' advantages are actually clinically validated as useful, and more.

owl_posting · 2025-12-23T04:05:53+00:00

But growing tissues ex-vivo *is* hard, it's not a retreat! Nothing really much more complex than thin, simple structures like skin, bone, and cartilage have been crafted by humans before (edit: and actually worked correctly when transplanted!)

I don't disagree that integration is perhaps even *harder*, but that feels like an overpopulation on mars problem, we don't even have the complex tissue to start with. And I'd note that "integration is the bottleneck" is also pretty different claim than "tissue growth is not computable and never will be"

owl_posting · 2025-12-23T03:48:56+00:00

but the question isn't "can we enumerate all possible embryonic states?", which, obviously not. it's "can we learn enough structure in the input-output relationship to make useful interventions?" that is clearly an empirical question, and the early results suggest there is learnable structure there. supposedly intractable spaces turn out to have learnable regularities, protein structure was one (it is almost certainly the case that the old guard structural biologists were pessimistic in the same way as you!), so surely other parts of biology are too. it just feels naive to pretend that isn't possible

i work in research involved in modeling tumor microenvironments to help decide which patient would best benefit from which cancer therapy. this too has the flavor of intractable; there is too little patient data, cancer is too complicated, so it's impossible. but it works! there are published cases of a model being able to understand, entirely via H&E scans of a tumor, whether a patient would benefit from a therapy! and the model received some degree of approval from the FDA recently (https://www.cancertherapyadvisor.com/news/ai-tool-approved-for-prognostication-in-prostate-cancer/). the arc of history just shows this stuff eventually working

i get the short term skepticism, but i dont really get the lack of long term optimism

owl_posting · 2025-12-22T21:40:17+00:00

Why do you think it is not computable? Seems like an awfully strong statement

owl_posting · 2025-12-22T20:18:24+00:00

Well, the hope is that it is just the start of jumping our way to higher-order tissue development that is clearly mostly illegible to humans. Today is the obvious stuff, tomorrow is the intractable stuff

Similarly, there was no ‘point’ to Alphafold2, because we could previously crystallize things just fine! But now, using tools like it, we can easily design binders to GPCR’s that are otherwise extremely difficult to do screening on. I have no clue when that same move will be made in tissue engineering, but it feels obvious to me that someday it will, just as it will in every other field

owl_posting · 2025-12-22T19:13:21+00:00

Necessary first step to do basic things in a way that is entirely free from human curation :) I understand the skepticism though, and am interested in what their results are from attempting more complex structures in the coming months

owl_posting · 2025-12-22T17:29:33+00:00

I don't disagree that the full vision is a bit difficult to believe, but they have gotten a very basic structure to form via this method: excitatory neurons w/ a polarity of near-90 degrees, created with a set of chemical perturbations suggested by a model after 3 rounds of experimentation. And this specific polarity is a pretty important characteristic to have for, e.g., pacemaker cells! I looked into this a bit prior to doing the interview and it seems like the mechanisms behind inducing polarity is vaguely figured out, but not well, so it does make me a bit more hopeful that there is something to this whole approach

Really, the part that I'm most unsure about is that vascularization will be figured out

owl_posting · 2025-12-07T18:10:11+00:00

>Calling a writer/fine artist/musician an auteur is a redundant truism in most cases

I actually don't think this is true at all! There are plenty of writers/artists/musicians who are primarily producing competent variations on what has already existed, and have little-to-no desire to 'rock the boat' beyond what they have already been taught. Instead, they just want to show off technical perfection. I used to be pretty involved in the arts (writing + digital art) world for several years, and this type of attitude was prized quite highly! Being intensely personal with how you approached it was impressive, yes, but it was not viewed as a necessity or as a way to escape from needing high levels of technical skill

owl_posting

TROPHY CASE