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Yes, it's very elegant! It's one of those things you wish you had thought of yourself. Kudos to these guys for being first.

Sometime after 685 AD, they invented spaces between words. All text - in Latin to that point, mostly - was written in scriptio continua.

All sorts of ambiguity and hilarity would ensue; to be a good writer, you needed to ensure that words didn't bleed together and form incorrect meanings in unintended combinations. If you lost your place when reading, you'd have to know generally where you were in a scroll, and restart from a place you remembered.

Kinda crazy to think how difficult it would be to cross reference things and do collaborative research with no spaces or pages.

Many times obvious things are only obvious once you see them. Like roller suitcases.

The early printing press was probably focused on short few page documents (an increasing scale), and it wouldn't be surprising if page numbers were a solution to help printers not mix up pages.

I can see how it wculd take that long to realize it would be nice to have a way to tell people which page to look at in their exact copy of a book.

If you live near a community bio lab see if you can join up and take some classes to learn some basic lab techniques. And some sort of intro bio class via mooc/textbook/local college class whatever if you can but community lab is honestly a great place to start if you have one.

The main thing to keep in mind is that all the stuff that involves analogies between software and biology is almost universally a bullshit oversimplification that you can safely ignore. It's just that software is so profitable and there's so much vc money in it that there's a ton of pressure to be like "oh we can program biology like we program computers." We can't - we invented computers but didn't invent biology. Biology is the end result of 4 billion years of unchecked entropy - it's a chaos system, non deterministic in the wildest ways, impossibly complicated, and yet something we are getting astonishingly good at understanding and engineering.

Basically, all the biologists that started companies that were like "we can program biology like we can program computers" are bankrupt now.

On the other hand, the computer scientists that respected the nature of biology and pushed the limits of computing to develop Alphafold - giant models trained on the full complexity of biological data - finally created computer systems that could handle biological systems like protein folding at an extraordinary level of capability. They won a nobel.

Possibly not what you're asking for, but I wrote a generally-accessible intro to why it can be tricky to assemble many DNA fragments with "Golden Gate Assembly", a mainstream method which relies on short sequence overhangs. The Sidewinder method discussed in this thread aims to solve that "short overhang" problem.

https://zulko.github.io/bricks_and_scissors/posts/overhangs/

We’ve been able to do this type of nucleotide 3D engineering for a while. I used to use large DNA branched complexed fluorophores to label cDNA back when I was in grad school. They were more or less mixed of DNA that self assembled into larger hairballs.

But branched DNA is really interesting. It’s a bit hard to get my head around. We spend so much time thinking about DNA in the 2D sequence sense, it’s easy to forget that it exists in 3D space.

I’m honestly not sure how different this really is to the traditional ways of doing this (with custom oligos). The common set of large self-hybridizing oligos is definitely easier, but you still have to have compatible tag overhangs between your two fragments. Meaning, it isn’t quite as universal and you’ll still need work to pair the fragments together. But where I think it might be useful is if you have a set of common hybridizing pairs that can be easily located onto the custom flanking oligos. You’ll still need some sequence analysis to get your custom oligos, but it would make the process more “standardized”.

I think the main bonus here is the self correcting selection… that you only end up with matching pairs linking together, so you could really have a mix in a one tube reaction that links many kilobase fragments together. That’s quite nice. And useful. And still cool.

One thing that is interesting is that this is another step towards getting the “writing” step of DNA analysis better. For the past 50+ years, we’ve developed all sorts of tools for reading DNA. It’s only really been the past 20-ish or so that we’ve had tools for writing. And now we can write longer chunks. That’s all a good thing.

Not sure I think it’s revolutionary (yet), but that’s a university PR release for you! I’m still thinking about the paper.

> using complementary overhangs and toehold sequences to generate a 3-way heteroduplex, ligate knick, and then remove barcode duplex

At first I thought this was about olympic figure skating, but after a bit of googling I think:

Complementary overhang - https://en.wikipedia.org/wiki/Sticky_and_blunt_ends

Toehold sequences: https://en.wikipedia.org/wiki/Toehold_mediated_strand_displa...

Ligate (ligase?) knick (nick?) - https://en.wikipedia.org/wiki/Nick_(DNA)

Barcode - https://en.wikipedia.org/wiki/DNA_barcoding

Heteroduplex - https://en.wikipedia.org/wiki/Heteroduplex

I don’t think PCR is necessarily relevant here. I had the impression that this would be lost useful at linking multi-kb fragments together. If we are looking at sizes much above 2kb, PCR is going to struggle to generate full length fragments efficiently.

I didn’t see this technique as having DNA modification per-se, but a novel way to managing the hybridization process. It’s stock (well engineered) oligos, if I read it correctly.

pcr amplifies all sequences, correct or wrong, no? and as I understand it, it works on short snippets the best.

Intuitively I agree some kind of selective amplification should be able to correct for the mistakes. But I think it will be complicated. Because the filtering process needs to be much more complex. It can’t just chemically match to a known subsequence - you won’t know where the mistake might be in a long sequence.

Probably AI in the sense of what Google DeepMind has been up to with the protein folding and other biological simulations, instead of the LLM variant of AI.

You don't need to synthesize an entire bacterial genome from scratch to do this. You can just insert them one at a time into existing bacteria. Or just give them plasmids. Anyway, the ability to achieve the outcome you're describing has existed for decades.

The ease of this "just" is the most concerning thing in the context of humankind's survival.

Is there a gene to avoid getting addicted to doomscrolling? ;-)

There is no way it is just "just". And we should start from simpler stuff like vitamin B12, C and D.

Imagine if we could turn our bodies into perfect spheres, and then adjust genetic beauty preferences to match it.

Oh if only science was not constrained by ethics.

I can already see the people protesting against the creation of space marines.

It was known in 2006 but rediscovered recently: https://patents.google.com/patent/US20060281113A1/en

It's a lot like TikTok, right? It's a very simple concept: immediately produce customized video recommendations taking into account even the most recent interactions.

You just need a way to pack the TikToks into blank data centers.

(Note: blank data centers is a concept that kind of sorta makes sense. A blank cell doesn't make any sense at all)

> Now we just need a way of packing the DNA strings into blank cells reliably.

Huh, I kinda assumed we'd already done that part with Dolly the sheep. But I'm not a biologist, I just saw headlines.

They have a nice simple explanation. But the biochemistry of it I’m guessing is anything but simple. I’ve never heard of three way junctions in DNA before. I wonder how new those are. And designing the molecules to do the matching and splicing must have taken a long time.

"just"