koeng

It’s hard to see how it would be evidence based if the evidence’s premise is fundamentally flawed - just in such a niche way that people not in my field wouldn’t be able to see it. They’re kinda preying on the fact that people like you can’t see it, and that’s sad.

No. But I feel like it is unlikely I'll find much value in it. Part 1 being on the Venter work does NOT inspire confidence at all. Not to dismiss them - they're great I've worked with them on a couple projects - but it frankly doesn't have anything to do with abiogenesis. The other fact that lots of creationists like it doesn't bode well either.

Like, of COURSE the Venter cell looks too complicated to originate from raw chemicals! The lineage it evolved from was far more complex, and Mycoplasma underwent minimization. Minimal life also does not equal simple life, or life that was most probable to arise from chemicals. Just a stupid premise, really.

There was an RNA molecule or molecules that could make more of themselves (probably really poorly, at first)

> where random gene modifications are just not probable enough to drive evolution. 3 billion DNA pairs cannot evolve randomly, there is not enough time and matter in the universe to randomly try successful generations of life forms.

As a biologist, I don't think this really follows. From my perspective of studying life, 3 billion DNA pairs can definitely evolve randomly - it's not even really that hard. Eukaryotic life just happened to get that because the fitness deficit from the retrotransposons weren't too bad. On the contrary, I can't actually see how bioelectric could drive evolution - only the creation of more complex structures

I'd love to see some benchmarks on your fastmath package

Teal can't be total. The generics can get real annoying, I noticed. Still, was worthwhile to use for the most part.

I've had very good experiences with swing dancing. People are so nice (LindyGroove in Pasadena). No pressure, and everyone is very accommodating to newbies. I'm not sure why, but there is a very high percentage of engineers.

Eh, I think I disagree with this. The point is that I can make very complicated libraries in Teal, and those compile down and are usable in lua scripts. This is where I actually used it - very simple scripts, very large and complicated library imported into those scripts. If you really need to prototype, just use lua, not teal. I've never found prototyping in teal to be a problem though.

On the other hand, I absolutely despise type annotations as comments. There is something so unclean about that - if I want a readable library, I want there to be type proofing all the way down. No switching between static and dynamic.

Nope, you can embed it. Teal is written in teal, and compiles down to lua - so you can simply put teal as a lua dependency. I used it with gopher-lua (Golang lua environment). https://github.com/teal-language/tl/pull/523

I’m learning swing dancing. It’s been humbling.

It’s humbling because all my life, I’ve been really good at technology - I specialize in biotechnology and manipulating DNA, but am also fluent in programming (mainly python, go, lua) and am able to build hardware - even helped run a robotics startup for a while. Anything related to technology and science comes easily and naturally to me. This isn’t to brag, but just a fact that learning things has mostly been something I do way, way faster than my peers.

But I’ve never danced before, or done anything that required that particular skill set - then realizing I’m real bad at it. Seeing all my peers learn faster and be better, with the same amount of study and practice time, and really trying my hardest and just not being good at it. I’m really thankful for this experience! And I really enjoy dancing, and will definitely keep doing it!

I’ve used teal before, the statically typed Lua that is mentioned at the end. It’s actually really good! There are some limitations (especially around generics) that can be annoying, however. Overall, I really enjoyed using it and would use it again.

Testing Elicit gave me quite a bit worse results than using PaperQA by futurehouse. While paperqa could understand a bit of the nuance of a scientific query, elicit did not.

Too bad the internal paperqa system at scihouse isn't available for public use...

I got a tube of this probiotic. They asked me not to sequence it, but I'm a little suspicious of putting it in myself, so trust-but-verify (probably Nanoporing). I literally cannot see why sequencing it is a "dick move", so I think I'll be doing it anyway.

I do not buy that it is dangerous. However, I haven't seen any statistics showing the frequency of mutacin-1140 or its efficiency. Back in 2015 when I was a teen I did an experiment using colicin V (an E.coli one - I was planning on engineering E.coli Nissile to replace my current gut E.coli with something more fun. Got kicked out of the science fair for that one - https://keonigandall.com/posts/colicins.html ). Turns out, you need a sizable portion of the population to get takeover. I haven't seen ANY data on the population percentage necessary for takeover with this strain. Nor have I seen statistics of its natural occurrence percentage.

I wanted to modify the strain to have GFP expression, so I can have my own little engineered biome for myself that is showable at parties and such, but it looks like they removed comE :( will have to start from an original strain instead, I guess.

Definitely interested in this for your wasm Go bindings!

Hmmmm, I don't know if I buy their claim of primary endosymbiosis being so rare.

Almost all insects have heritable endosymbionts. https://doi.org/10.3389/fphys.2013.00046

What is the search engine that it uses?

The reasons I ask for a counter example is because the number of “what ifs” are pretty much unlimited and easy to come up with, whereas I have to do a lot more thinking to answer them. It’s asymmetric and gets tiring

Answer is: no, not proven to be perfect. Most source is closed for the software. There is no specification. Never been a red team trying to break it. Unknown if it’s ever stopped any threats. There is no requirement to do it, and it’s all voluntary (though pretty much all synthesis providers do it). Mostly they just hash kmers and translations thereof and scan a pathogens/functional database. So implementable in a simple KV store for the most part. The bigger problem is false positives, and most work is done in de-shittifying the upstream pathogens data.

Here’s a good paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988571/

Last I checked all the groups charged a lot of money for access, unfortunately, and I’m not really big enough to join a group like the International Gene Synthesis Consortium :(

can you give a specific instance of a sequence that would be dangerous in a cloning strain and not screenable?

Thanks!

Personally, I think the threat from the biologics itself is a little overstated. If COVID was released from a lab (I think it was natural), it was most likely due to bad governance and management of the lab. For DIY things - most DNA can be screened. I have had companies offer screening services for about 50k-100k a year. I can't afford that! So hopefully a free service or something near to that comes online.

The oldest sequenced DNA is 1.6 million years old. In the right conditions, it lasts far longer than pretty much any storage method right now. Plus I also sometimes store things in Bacillus subtilis, which is very hardy https://keonigandall.com/posts/sporenet.html

No, I know pretty much everything I synthesize. Once I don't, I'll just connect some screening software.

I sometimes derive protocols from off-shelf ones, but pretty much everything beyond that is in-house. Most off-shelf protocols work for 1 sample in 1 tube - I had to adapt them to working on 1 plate of 384 tubes (and get those to work with robots). There is a significant amount of robotic code that I use, and a few custom protocols that are from a random obscure scientific paper in 1980s or 1990s

A bespoke freelance industrial adhesive maker sounds like such a niche job, that's awesome. I would love to see a hackernews-type post with details of how he thinks about making a specific adhesive.

I never went to university or anything, but did work for 4 years at UCI in directed evolution / mitochondrial engineering, then 3 years at Stanford on the FreeGenes project (got invited to work at both). Barely passed high school cause I didn't care about my classes there.

I use restriction enzymes + ligase to cut DNA, then paste it back together at specific sequences. It's pretty simple honestly! https://www.khanacademy.org/science/ap-biology/gene-expressi...

The key is doing that at an industrial scale, reproducibly, with hundreds to thousands of plasmids at once. Becomes less simple. You encounter bullshit problems with biology, which I guess is valuable because it makes a moat!

I found a virology textbook at the local Catholic book fair when I was in 6th grade, got hooked, teacher in 7th grade let me order GFP transformation kits to the school that I could do at home, then off to the races from there. I was in this article if you're interested in more deets: https://www.nytimes.com/2018/05/14/science/biohackers-gene-e...

That's how Twist/Agilent do oligo pool synthesis (and Dynegene now). I'm pretty interested in the Genscript / Avery digital method of electrochemical synthesis. Turns out those pools ain't good enough to be used in a biological context, which is where I come in - I can assemble them well into sequence perfect stuff

I can share a few things! (but definitely not all)

- One is finding different T7 RNA polymerases with unique properties by manipulating the backbone. They can be used for things like in-vitro RNA production for vaccines - Another is synthesizing a phage that has been sequenced for a specific organism, but that the samples are now lost of. So resynthesizing that genome from scratch - A different project (personal one) is building a DNA parts toolkit with standardized DNA parts so you can combine em together like legos. Pretty much nowhere but FreeGenes has open source genetic parts (I used to run that project), and I think open source genetic parts need to be in the world

I’ve been working on a synthetic DNA assembly company. Basically, I figured out how to assemble DNA for people at a fraction of what it normally costs, so they give me a sequence, and then I make it in real life for them, then ship it to them.

Most of my customers have been AI protein designers, ironically. Turns out SOMEBODY has to wrangle atoms in the real biological world and that’s me!

After almost a year of work I finally smoothed out all the kinks in the process, so can now go from a design to synthetic DNA in a cell in about a week (not counting oligo pool synthesis time). I can do about 600,000bp per week, which is large enough to synthesize the smallest bacterial genome (each week), tho I only do about 1000bp fragments. I’m also completely bootstrapped and self funded, and only get help from my several opentrons robots