They don't use oligo pools - "This capacity may be adapted to use large oligo pools to substantially reduce the cost per construct45 but requires further engineering to account for the formation of the unintended Sidewinder heteroduplexes before assembly and the higher truncation rate of pooled oligos"
This absolutely destroys any unit economics when it comes to DNA synthesis. Oligo pool synthesis isn't 10x cheaper, it's 100x to 1000x cheaper than individual oligo synthesis.
So what they really have is a good way to do DNA assembly from synthesized oligos; fair. But we have that: GoldenGate can do 40 part assemblies, hell it can do 52 part assemblies, and you CAN use oligo pools - https://pmc.ncbi.nlm.nih.gov/articles/PMC10949349/ (there are a couple enzymatic properties which allow this, mainly that you can use full doublestranded DNA, which you can make with a PCR. Can't make these overhang guys with a PCR).
We've even found that with some GoldenGate enzymes, the biology somehow breaks the current models of the physics of ligation by being so efficient - https://www.biorxiv.org/content/10.64898/2026.01.31.702778v1
Their gels do look really good, I'll admit. I can imagine circumstances (exception cases) where this would be better. But not only is this kind of thing for 99% of cases has already been available for many years while being orders of magnitude cheaper (plural).
It is super clever and exciting. Note that people have been able to assemble short (<100 bases) DNA oligomer fragments of synthetic DNA into longer fragments using "splint" oligos since forever. But in this case, each splint has to be custom engineered to only bind to the junction of interest (in practice it is pretty tricky and expensive to do this.) These guys figured out a way to use engineered sequences to make the match, and used a clever (but also more or less standard) way to chew up the engineered stuff, leaving behind only the desired long assembly with no scars at the end of the process.
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.
https://commons.wikimedia.org/wiki/File:Pantheon_Rom_1_cropp...
The parent article mentions that binding the pages of the first bibles in the correct order, in the absence of page numbers, was an extremely tedious work.
That is why page numbers have invented many years later, exactly as you say, "to help printers not mix up pages".
It's an interesting idea. Remember they printed large sheets containing many 'pages', I think even in different orientations, which were then folded and the ends cut to produce a nice orderly codex for the reader. They were printing in a different order than the one you read in.
I do think they numbered the large sheets or similar, and you can find old books that retain that number, but I don't recall what it is called.
https://en.wikipedia.org/wiki/Gutenberg_Bible#/media/File:Gu...
Hindsight is 20/20 , lol. There are so many obvious, effective constructs and functions in modern English, we kinda miss the absolute janky mess of hacking and tradition and arbitrary rules and facepalm moments that went in to the last 1500+ years of development, let alone the tens of thousands of years prior.
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.
I'm wondering if I could find a fun weekend project in alphafold just to see what it's like.
Are they really? Is this just limited to some very specific areas with an active biotech scene?
https://zulko.github.io/bricks_and_scissors/posts/overhangs/
“ Guided by the removable DNA page numbers, Sidewinder achieves an incredibly high fidelity in DNA construction with a measured misconnection rate of just one in one million, a four to five magnitude improvement over all prior techniques whose misconnection rates range from 1-in-10 to 1-in-30.”
I wonder if this is even a problem, since you could amplify the correct sequence with PCR afterward.
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.
You're correct that PCR has a limited max length, but it is longer and cheaper than vanilla DNA synthesis.
Yes, someone has attempted in the last to breed or alter for specific traits, we’ve cloned many kinds of life, and if there was extraterrestrial life here, someone probably mixed it with humans and animals.
But the pace of this is not going to increase anytime soon, if history is a judge. CRISPR was scaring people years ago when publicized, but those worries were unfounded and so shall these be. Life is much harder than coding apps.
Sidewinder itself sounds neat.
Has anyone dabbled in hobbyist genome editing and DNA synthesis or is this something that requires a huge pile of capital?
They don't give much details on how the barcode duplex is removed though. I guess ultimately the barcode duplex strands can just be melted off and the ligated strand can be used to template off of.
If this can be made into an easy to use kit, can really make vector generation much easier and hopefully not locked into proprietary systems.
I can imagine a company that bioinformatically generates libraries of common long oligos with corresponding barcode and allow end-users to select oligos to modularly ligate together in a one pot reaction. Cool stuff.
lol every time I ask Claude to whip me up a protein for this or that I hit a guardrail. I love the idea that some internet random is untrustable with an ai hallucinated amino acid sequence, as if I could encode that and stick it into my ecoli farm out back
https://web.archive.org/web/20260121201045if_/https://www.na...
It's instead a way to stitch together longer sequences of DNA. Still very cool
Just include the genes for extreme-cold or extreme-arid climates. Or the genes for low oxygen environments, or even for metabolizing useful things from eating rocks. Or from spending 24 hours a day in salt water.
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)
Huh, I kinda assumed we'd already done that part with Dolly the sheep. But I'm not a biologist, I just saw headlines.
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.
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
Right? I wouldn't expect genes for heat/cold tolerance in other organisms to necessarily be useful in humans. They work by mechanisms that are useful for that organism, but humans have our own set of problems.
It's like saying you can strap a jet engine on to a tractor and expect farm work to massively speed up. No: the machinery doesn't translate for a clean swap like that.
Just tell your car to drive you to the airport. On the way just tell it to play that song you like.
I can already see the people protesting against the creation of space marines.
The same scientists who cry about ethics, have happily experimented on mice and guinea pigs in their labs, even if it causes the deaths or distress of those little sentient beings.
Mutations/mutatives like Halo's Master Chief and Marvel's Super Soldier serum won't remain sci-fi for much longer, methinks.
TikTok's 'Addictive Design' Found to Be Illegal in Europe: https://news.ycombinator.com/item?id=46911869
Gen Z less intelligent than millennials: How skipping books and doomscrolling are taking a toll on cognitive abilities: says Dr. Jared Cooney Horvath: https://www.msn.com/en-in/news/India/gen-z-less-intelligent-...
The Polymerase Chain Reaction
https://www.nobelprize.org/prizes/chemistry/1993/mullis/lect...
The whole context of written words had so much implicit process and knowledge and institutional memory, compared to now when we have petabytes of throwaway logs and trivial scratchpads for software running on a "just in case I might need to figure something out" basis. I'd love to see a written word graph over time, starting ~4k BC to now. And the complexity and diversity of those automated words are going up like crazy since LLMs.
It's not uncommon that adults do something similar and run a community workshop with whatever the members are interested in.
The field may not be fully constrained by ethics, which is just a way of saying that the work is done by people and people have varying ethical bounds, but from what I saw many of my colleagues were highly ethics driven.
I remember one Russian colleague who smuggled blood products out of Russia so they could be tested for HIV. Because the Russian government refused to help these patients. The man risked his life to help HIV sufferers.
Ethics is best when matched with courage, if a person is willing to put their life on the line for their beliefs.
Also noting that in the western world, experiments generally need approval of an ethics board before proceeding. That board's sense of ethics might make different judgments than you on, for example, mice experiments, but there is a big difference between "not constrained" and "some of the constraints are different than what I would choose".
where in this case, the ethics boards decided that provided a certain risk/reward barrier is crossed, and that the animals are otherwise treated well, sacrificing mice to improve human health is just fine.
That is an ethics based decision that was debated for a long time. And maybe should continue to be debated, there is real value in your stance that all beings are sentient and this demands a level of care.
I do understand what you mean, and I do comprehend that animal testing cannot be avoided for scientific advancements to help and progress humanity.
But I have a simple motto I want to adhere to (it is very hard though, to practice it in principle and action daily): Ethics is best when it is for the good of humanity, without being bad for Earth.
In recent years, I am starting to feel humanity is sharply veering away from its basic ethics (and the first ethic must be to not shit where one eats - but hey, we are actively aggressively destroying the only beautiful bountiful planet we know of, that can support humanity), and doing whatever the top richest most-powerful elites want.
And this unbridled greed and apathy is going to sow the seeds for the downfall of humanity, I'm afraid. At the cost of our precious Earth and its other denizens who share this planet with us humans.
There has been a catastrophic 73% decline in the average size of monitored wildlife populations* in just 50 years (1970-2020), according to World Wildlife Fund‘s (WWF) Living Planet Report 2024.
https://www.worldwildlife.org/news/press-releases/catastroph...
https://www.bbc.com/news/articles/c5y3j0vzpl3o
Forests around the world disappeared at a rate of 18 soccer fields every minute, a global survey found.
https://www.nytimes.com/2025/05/22/climate/deforestation-wri...
Our generation is the last one that can still save the wild forests of the Earth, which help us cope with the climate crisis and preserve the biodiversity of the planet. A new study by Greenpeace Russia and the University of Maryland has shown that if urgent and effective measures are not taken to preserve wild forests, most of them will disappear in the next 20 years.
https://www.greenpeace.org/international/story/51810/wild-fo...
Volkswagen (the same megacorp that did the infamous Dieselgate/Emissionsgate scams) forced monkeys to inhale exhaust from its automobiles, to try to show that fumes from current models (the cars, not the monkeys) were less noxious than previous models.
https://www.msn.com/en-us/science/sociology/20-of-the-most-u...
https://en.wikipedia.org/wiki/Volkswagen_emissions_scandal
I guess this cannot be termed as "torturing animals" in the "name of science".
We humans also inhale vehicular exhaust fumes, don't we?
Oh wait, I forgot. Monkeys don't drive cars.
Or do they? https://m.youtube.com/watch?v=XW5NLeGEo94
It's been built up over centuries where new innovations and shifts in perspective often create new kinds of notation, but those most frequently just get tacked onto whatever else is already standard and the new notations almost never actually supplant the old.
AFAICT we haven't really had a big shift in fundamental mathematical notation in Europe (and its colonies) since Roman Numerals (CXXIII) gave way to Arabic (123) numerals four hundred years ago. 8I
Your history is a little confused. Arabic numerals came into use in Europe as early as the 13th century (introduced by Leonardo Fibonacci), but most other mathematical notation like "=" or or "√" didn't show up until the 16th or 17th century.
