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Invention of DNA "page numbers" opens up possibilities for the bioeconomy
- smackeyacky 8mo agoOk that’s it for me. Selective breeding via BLUP at least had a speed limit, this is going to end with cronenburg brundlefly creations.
- unsupp0rted 8mo agoThis is probably the only way "humans" are going to colonize any planets other than Earth. And probably lots of new places on Earth too. 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.
- wartywhoa23 8mo agoThe ease of this "just" is the most concerning thing in the context of humankind's survival.
- vee-kay 8mo agoThen I recommend you don't find out what "Project Molecule" intends to do.
- imzadi 8mo agoCare to enlighten? Google has nothing meaningful.
- vee-kay 8mo ago[flagged]
- vee-kay 8mo ago[flagged]
- vee-kay 8mo ago*collusion
- 9dev 8mo agoThese files are a never ending quell of evilness. It’s really fascinating. One day people are going to realise the upper 1% are just that—very few….
- vee-kay 8mo ago[flagged]
- mmooss 8mo agoFor the most part, they only have the power others give them.
- wartywhoa23 8mo agoSlight correction: the power others gave them a long time ago, and now nothing can help those others take it back without uprooting the whole civilization in the process. Current power is a malignant formation too advanced to heal without destroying the whole organism. Or so it seems, I'd really like to be wrong here.
- mmooss 8mo agoIt's not a slight correction, those claims are the exact problem - the propaganda of the powerful: Give up, there is nothing you can do. People in democracies can easily vote to change where power lies (that is, power lies ultimately with the citizens), if that's what they want, and it's not hard to see how: The current situation is highly unusual for democracies; there is a long history of what to do and how to do it. A major reason they don't do it is that they keep reading and believing they are powerless.
- wartywhoa23 8mo agoThanks for the heads-up!
- Windchaser 8mo ago>The ease of this "just" is the most concerning thing in the context of humankind's survival. 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.
- Traubenfuchs 8mo agoOh if only science was not constrained by ethics. I can already see the people protesting against the creation of space marines.
- whycome 8mo agoNo laws on mars
- vee-kay 8mo agoScience has never been constrained by ethics. 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.
- melagonster 8mo agoAnd save human life at the same time? Experiments are not just about torturing animals; people spend a lot of time optimizing for experiment design.
- vee-kay 8mo ago[flagged]
- vee-kay 8mo agoHey, did you hear about the Volkswagen Monkeys? 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-unethical-scientific-experiments/ss-AA1U8fqH https://www.msn.com/en-us/science/sociology/20-of-the-most-u... https://en.wikipedia.org/wiki/Volkswagen_emissions_scandal 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 https://m.youtube.com/watch?v=XW5NLeGEo94
- vee-kay 8mo agoIs there a gene to avoid getting addicted to doomscrolling? ;-)
- vee-kay 8mo agoRelevant and topical.. TikTok's 'Addictive Design' Found to Be Illegal in Europe: https://news.ycombinator.com/item?id=46911869 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-than-millennials-how-skipping-books-and-doomscrolling-are-taking-a-toll-on-cognitive-abilities/ar-AA1VOq8a https://www.msn.com/en-in/news/India/gen-z-less-intelligent-...
- krzat 8mo agoImagine if we could turn our bodies into perfect spheres, and then adjust genetic beauty preferences to match it.
- Windchaser 8mo agoSeems like a heat dissipation problem
- throwaway198846 8mo agoThere is no way it is just "just". And we should start from simpler stuff like vitamin B12, C and D.
- unsupp0rted 8mo agoEverything is “just” eventually. Just tell your car to drive you to the airport. On the way just tell it to play that song you like.
- wartywhoa23 8mo agoAlas, one's happiness (as in genuine inner wellbeing, as opposed to the consumption-based external one) is no "just" matter, and never will be.
- jryb 8mo agoPaper: https://www.nature.com/articles/s41586-025-10006-0 https://www.nature.com/articles/s41586-025-10006-0
- jurgenburgen 8mo agoThe article mentions AI multiple times even though the invention appears to have nothing to do with AI. I guess it’s important to have it as a marketing buzzword. 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?
- maxboone 8mo agoProbably 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.
- krzat 8mo agoCool. I wonder how long until we are able to steal anti-cancer genes from whales.
- trebligdivad 8mo agoThat page numbers in books were only invented 50 years after the printing press is a fun snippet from the article
- swalsh 8mo agoMany times obvious things are only obvious once you see them. Like roller suitcases.
- bookofjoe 8mo agoSee also: the wheel
- ssivark 8mo agoThe 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.
- adrian_b 8mo agoYour hypothesis does not match history, because the early printing was focused on things that had a potentially large market, which at that time meant books like The Bible, with a lot of pages. 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".
- observationist 8mo agoThe Gutenberg Bible was one of the first mass produced books - no page numbers on early copies. https://en.wikipedia.org/wiki/Gutenberg_Bible#/media/File:Gutenberg_Bible,_Lenox_Copy,_New_York_Public_Library,_2009._Pic_01.jpg 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.
- nullbyte808 8mo agoSuch a simple concept took this long to discover? Now we just need a way of packing the DNA strings into blank cells reliably.
- pc86 8mo ago"just"
- ben_w 8mo ago> 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.
- oofbey 8mo agoThey 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.
- epistasis 8mo agoIt'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)
- Metacelsus 8mo agoIt was known in 2006 but rediscovered recently: https://patents.google.com/patent/US20060281113A1/en https://patents.google.com/patent/US20060281113A1/en
- jycnaw 8mo agoMovies that come to mind that involve genetic building at this level are Gremlins 2, The Clone Wars, and some in the Alien franchise. 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.
- nullbyte808 8mo ago[flagged]
- throwaway89201 8mo agoWhat's the source of the text? It seems to be either a copypasta from a journal article or LLM-generated (and not your own text).
- direwolf20 8mo agoLLM–generated summary. A human summary wouldn't specify the temperature used because it's irrelevant.
- pcrh 8mo agoI briefly scanned the paper. The above summary is garbage. For a biologist, a summary might be like this: pcr fragments are generated with short reverse complementary sequences added to the end of one fragment that match that at the begining of the next to-be-joined fragment. These will anneal to create a cross-shaped DNA molecule. The short arms of the cross being the complementary sequences. Like so: ======∥===== The short arms can then be processed-off to leave behind the now-longer fragment. The process can be repeated using different reverse complementary sequences between each fragment, the "page numbers" referred to.
- oofbey 8mo agoSo do the complementary sequences naturally bind to their neighbors? So you just mix the “pages” in a soup for a while until they all find their friends. And then the custom enzyme (or what is it) just slices off the three way junctions? Really clever.
- pcrh 8mo agoThat's right. It's one of those elegant solutions that just seem so obvious once they're presented. But this lot did it first.
- jackconsidine 8mo agoSaw the headline and thought we were coming full circle on GEB -- a discovery of page number mechanisms in DNA functioning like GOTOs in code. It's instead a way to stitch together longer sequences of DNA. Still very cool
- biophysboy 8mo agoChemical modifications of DNA are so amazing, and underpin so much DNA related research and engineering. Illumina and Moderna would not exist without DNA mods. It’s very cool that the set of tools is expanding further! “ 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.
- codesnik 8mo agopcr amplifies all sequences, correct or wrong, no? and as I understand it, it works on short snippets the best.
- biophysboy 8mo agoIt amplifies sequences that contain the two primer sequences on each end of the target. So if you had synthesized sequence XYZ with some mistakes like YZX, then you could target X and Z and purify. You're correct that PCR has a limited max length, but it is longer and cheaper than vanilla DNA synthesis.
- bookofjoe 8mo agoKary B. Mullis Nobel Prize lecture Nobel Lecture, December 8, 1993 The Polymerase Chain Reaction https://www.nobelprize.org/prizes/chemistry/1993/mullis/lecture/ https://www.nobelprize.org/prizes/chemistry/1993/mullis/lect...
- oofbey 8mo agoIntuitively 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.
- Kirr 8mo agoVery cool, but may have some unexpected consequences. E.g., someone can probably use this to synthesize a bacterial genome containing every known drug resistance gene, and this is just the first thing that comes to mind. Possibilities for bioeconomy indeed.
- jryb 8mo agoYou 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.
- GlibMonkeyDeath 8mo agoWhat really blows my mind about this is that they are using off-the-shelf T4 Ligase to ligate the junctions. I figured this was going to be some tour-de-force of enzyme engineering, but nope, all the reagents are pretty much commercially available. 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.
- pcrh 8mo agoYes, it's very elegant! It's one of those things you wish you had thought of yourself. Kudos to these guys for being first.
- victor106 8mo agoFor someone in Software what is a good way to learn the fundamentals of this?
- zulko 8mo agoPossibly 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/ https://zulko.github.io/bricks_and_scissors/posts/overhangs/
- vikramkr 8mo agoIf 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.
- ramon156 8mo agoFollow up question (Not OP), would alphafold more be used to experiment with an already-defined theory that you have, or could you also make some toy projects (e.g. how people make projects around trading engines). I'm wondering if I could find a fun weekend project in alphafold just to see what it's like.
- oytis 8mo agoCould we better not?
- daemonk 8mo agoPretty cool technique using complementary overhangs and toehold sequences to generate a 3-way heteroduplex, ligate knick, and then remove barcode duplex. 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.
- omnicognate 8mo ago> 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 https://en.wikipedia.org/wiki/Sticky_and_blunt_ends Toehold sequences: https://en.wikipedia.org/wiki/Toehold_mediated_strand_displacement https://en.wikipedia.org/wiki/Toehold_mediated_strand_displa... Ligate (ligase?) knick (nick?) - https://en.wikipedia.org/wiki/Nick_(DNA) https://en.wikipedia.org/wiki/Nick_(DNA) Barcode - https://en.wikipedia.org/wiki/DNA_barcoding https://en.wikipedia.org/wiki/DNA_barcoding Heteroduplex - https://en.wikipedia.org/wiki/Heteroduplex https://en.wikipedia.org/wiki/Heteroduplex
- mbreese 8mo agoWe’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.
- koeng 8mo agoI work in DNA assembly and synthesis. Here is my take: 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/ 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 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).
- 1vuio0pswjnm7 8mo agoHere's the paper without the cookies https://web.archive.org/web/20260121201045if_/https://www.nature.com/articles/s41586-025-10006-0?error=cookies_not_supported&code=0d22745d-cfe0-4ab1-9d2b-5d8d9589b5fa https://web.archive.org/web/20260121201045if_/https://www.na...
- Metacelsus 8mo agoThe Church lab came up with this in 2006, sadly it never took off: https://patents.google.com/patent/US20060281113A1/en https://patents.google.com/patent/US20060281113A1/en
- kylehotchkiss 8mo ago> has made it possible to design genetic sequences encoding for diverse biological applications, such as proteins 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