[HN Gopher] Generative A.I. arrives in the gene editing world of...
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       Generative A.I. arrives in the gene editing world of CRISPR
        
       Author : msmanek
       Score  : 73 points
       Date   : 2024-04-23 16:25 UTC (6 hours ago)
        
 (HTM) web link (www.nytimes.com)
 (TXT) w3m dump (www.nytimes.com)
        
       | pointlessone wrote:
       | What can possibly go wrong if we let ChatGPT edit our DNA?
        
         | genghisjahn wrote:
         | Have you seen DNA? Mistakes and dupes and hallucinations all
         | over the place. Ever since Sherlock Crick and Doctor Watson
         | started meddling with it.
        
           | miraculixx wrote:
           | It's one thing to analyze it. It's an entirely different
           | thing to let a machine of dubious abilities create new DNA.
        
             | Wissenschafter wrote:
             | Isn't DNA in itself a machine of dubious abilities? It's
             | only functional because what functions is what survives,
             | imagine the amount of 'unsurvived' because of how shit the
             | code is.
        
             | yieldcrv wrote:
             | machines that undergo accelerate evolution, I would trust
             | them more under rigorous guidelines
             | 
             | I just need to be able to test the guidelines and results.
             | Clinical trial process to make an objective decision from
             | that point.
        
         | arcticfox wrote:
         | This model has nothing to do with ChatGPT other than
         | transformers. And as someone that could desperately use some
         | advances in gene editing, this lowbrow dismissal is
         | frustrating.
        
         | m3kw9 wrote:
         | And how does ChatGPT edit your dna
        
         | Mindless2112 wrote:
         | Have you seen how generative AI thinks hands work? Just a few
         | edits and reality can catch up.
        
       | mxwsn wrote:
       | Gift article (no paywall):
       | https://www.nytimes.com/2024/04/22/technology/generative-ai-...
       | 
       | Preprint:
       | https://www.biorxiv.org/content/10.1101/2024.04.22.590591v1
        
         | byearthithatius wrote:
         | Hey thanks:) That was nice of you
        
         | neuronexmachina wrote:
         | And their repo: https://github.com/Profluent-AI/OpenCRISPR
        
         | JoeH2 wrote:
         | Very kind of you! Thank you!
        
       | miraculixx wrote:
       | Reading their blog post I wonder if an LLMs is really the best
       | way to do this. If I got it right, they used the LLM to enumerate
       | potential protein DNA sequences. Does that really need an LLM?
       | Enumeration is not novel, nor are LLMs particularily good at it.
       | If you want to computationally parallelize the search in a large
       | enumeration space it would be much easier to simply, well, do
       | that instead of taking a detour via a statistical parrot.
       | 
       | In a nutshell this sounds more like a case of "we wanted
       | something with AI in the title".
        
         | mxwsn wrote:
         | It's not an English LLM, but a "protein" language model, where
         | tokens represent amino acids or nucleotides. Learning a
         | transformer language model on such data simply learns a
         | distribution over sequences of tokens. It's a fine approach
         | conceptually that in many ways is the "right" way or most
         | elegant method, and not a stretch at all.
        
           | devindotcom wrote:
           | I enjoyed the feeling when I made this connection talking
           | with a startup doing this a while back. It's just a different
           | "language" and although it's not a given that LLMs can
           | operate in it, it's a reasonable thing to try, and it turns
           | out they can.
        
             | dekhn wrote:
             | Personally I think it was obvious that LLMs were going to
             | be useful for protein modelling since the previous
             | generation used HMMs _very_ successfully. Pfam (a library
             | of HMMs for classifying proteins into preexisting known
             | families) is one of the most important resources we have
             | because of the power of HMMs to model sequential language.
             | 
             | I suspect we will need to move from sequential modelling to
             | graphical modelling to level-up again, though.
        
           | echelon wrote:
           | > Learning a transformer language model on such data simply
           | learns a distribution over sequences of tokens.
           | 
           | If statistical distributions can model higher level
           | polypeptide structure, then it could be useful.
        
         | swamp40 wrote:
         | Well hopefully it's trained on genetic DNA sequences and not
         | Reddit threads. If so, it should do pretty well predicting the
         | next sequence given previous sequences. There are probably all
         | sorts of undiscovered patterns.
        
         | changoplatanero wrote:
         | I think your intuition is off here. The number of sequences to
         | enumerate is much greater than the number of atoms in the
         | universe. You need a smart way to enumerate these and that's
         | what the LLM is for. The statistical parrot is not a detour its
         | a shortcut.
        
         | luckman212 wrote:
         | To be fair, having AI in the title landed it on the front page
         | of HN, so...
        
         | meowkit wrote:
         | The real power of LLMs is they can model anything as a
         | "language" given the right sequence training data.
         | 
         | Warning: the following is my opinion.
         | 
         | In the same way that MLP "neurons" are universal approximators,
         | it seems that LLMs are universal mappers.
         | 
         | They have the potential to help us organize and translate the
         | immense quantity of data being generated by modern methods in
         | all respective disciplines. We might create a model that
         | translates english to protein synthesis, and vice versa, which
         | would be pretty useful given my lay understanding of biochem.
         | 
         | To your point - this probably is NOT the best way to do this in
         | an objective sense. But to my mind we are hitting upper limits
         | as finite beings and need things like this, which utilize
         | native language constructs, to move forward.
        
         | dekhn wrote:
         | I don't have a direct answer to your question. My guess is that
         | LLMs are too limited to make truly great solutions in biology
         | but sequential modelling is a key component that will not be
         | replaced any time soon. For example, transformers were key to
         | AlphaFold's success, but they still needed many other steps to
         | make accurate predictions.
         | 
         | I worked on a predecessor to LLMs - HMMs for protein modelling.
         | They were, and still are for most people the best way to model
         | protein sequences. It's usually done as prediction, rather than
         | generation (IE, you use the model to classify an unknown
         | sequence into a known category, rather than asking the model to
         | generate new instances of a category). HMMs for proteins are a
         | bit stuffy, and they model local changes well, but struggle
         | with long-range interactions that LLMs seem to excel at (for
         | example, an HMM will do a good job of letting you stuff a few
         | more residues into a protein in a localized region such as a
         | hinge, but are not so great at modelling groups of residues
         | that are located far-apart in sequence space but close in
         | protein space).
         | 
         | One detail of the bitter lesson is, imho, that statistical
         | parrots are better than they "should" be, probably for the same
         | reason that mathematics is unexpectedly proficient in modelling
         | physics: to some degree, the models recapitulate the true
         | latent space of the underlying system well enough to generalize
         | outside the original observation space.
        
         | bglazer wrote:
         | First the search space is way too large for brute force
         | enumeration. We're talking like 10^300 combinations. Also the
         | hard part isn't just listing amino acid sequences, its finding
         | ones that do what you want them to. The only way to figure that
         | out is by testing them, which is difficult and expensive. So
         | you need an algorithm that is good at only listing sequences
         | that are likely to work. That's precisely what LLM's are good
         | at: finding patterns and sequences that are correlated in a
         | useful way
        
       | sharpshadow wrote:
       | I still consider biological life as the best 'robot' because it
       | can create more of itself.
       | 
       | As long as robots are incapable of recreation I don't see the
       | threat.
       | 
       | One could say all maschines today are infertile.
        
         | jprete wrote:
         | What about computer viruses?
        
           | r2_pilot wrote:
           | Computer viruses run on hardware they do not create but
           | merely hijack. Unless a virus took control of a semiconductor
           | fab, it's hard to argue that they are alive/reproducing in
           | the context of this discussion.
        
             | scarmig wrote:
             | Parasites do the same thing: hijack a piece of hardware and
             | use it to reproduce. Computer viruses have even formed a
             | kind of symbiotic ecosystem with blackhats: the scammer
             | provides resources to help the virus reproduce, and the
             | virus provides access to the scammer in turn.
             | 
             | In a way, all life hijacks hardware (the material world)
             | that it doesn't create to reproduce itself.
        
               | mewpmewp2 wrote:
               | Computer viruses need to get an ability to mutate by
               | themselves, improving the code overtime though.
        
               | ben_w wrote:
               | Simulated evolution is trivial to implement, but my guess
               | is also a bit pointless from the point of view of most
               | people writing viruses -- the viruses might mutate to
               | _not_ give them money.
        
               | scarmig wrote:
               | Those mutations would probably be favored by evolution,
               | if anything. They would attract less attention and allow
               | more focus on reproduction.
        
               | nyokodo wrote:
               | > Parasites do the same thing
               | 
               | Only analogously. The reality is that what we call
               | computer viruses are merely instructions running on a
               | computer and are not substantially distinct from the
               | computer in the same way that parasites or physical
               | viruses are distinct from biological tissue.
        
             | ben_w wrote:
             | > Unless a virus took control of a semiconductor fab, it's
             | hard to argue that they are alive/reproducing in the
             | context of this discussion.
             | 
             | It does not seem implausible at this point to imagine a
             | virus which gets to control some currency, uses it place an
             | order for parts to be assembled, delivered to a location,
             | connected to power, etc.
             | 
             | It is, in a sense, taking control by pulling the levers
             | supplied by our society. Is that alive?
             | 
             | I would say no, it is not 'alive'... but I would also
             | paraphrase Dijkstra: "The question of whether an AI or
             | computer virus is 'alive' is no more interesting than the
             | question of whether a submarine can swim."
        
           | karaterobot wrote:
           | I think of robots as being physically embodied somehow. I
           | don't think of a software program like a virus as being a
           | robot.
        
       | swamp40 wrote:
       | Imagine an AI learning from photos/videos of a person _and_ their
       | DNA sequence? And also a list of diseases, health records, etc.
       | Then asking it for predictions while giving it feedback
       | afterwards so it can tune itself.
       | 
       | You could even guarantee privacy. That would be some really
       | useful data.
        
         | paxys wrote:
         | You mean exactly what 23andMe tried to do, and failed miserably
         | at.
        
           | swamp40 wrote:
           | We are still early. Eventually you'll be able to change your
           | race, gender, add reptile eyes, regrow limbs etc. Has to
           | start somewhere. Need more data.
        
             | pharmaz0ne wrote:
             | Exactly. We should start building global database
             | connecting DNA with medical history.
        
               | swamp40 wrote:
               | Not a big fan? It could be provably private. You could
               | have a kit with a random username/password. It could be
               | done. People just have a bad taste from 23andMe.
        
               | dekhn wrote:
               | You mean, like UKBB and All of Us already do, but less
               | nationally focused? The approach seems fraught with
               | complexity due to the complexity of medical ethics, the
               | variation of national laws, and strongly-held nationalist
               | positions.
        
             | ronald_raygun wrote:
             | I can already change my race. I just check a different box
             | on government forms...
        
             | dekhn wrote:
             | I really, really wanted to see a new generation of tattoo
             | technology based on fluorescence and squid chromatophores.
             | However, for the time being, the vast majority of gene
             | editing will be for well-understood medical conditions
             | where all the alternatives have been excluded. Germline (or
             | even somatic) modification for recreational purposes or for
             | non-urgent medical reasons is definitely still considered
             | highly suspect by society as a whole, and I don't see that
             | changing overnight. Somethings still work better in scifi
             | than reality.
        
           | hanniabu wrote:
           | There was no privacy there
        
         | vessenes wrote:
         | I like this a lot; you could have a multimodal setup with a DNA
         | transformer, an image transformer and an LLM. Extremely
         | fundable startup.
        
       | a-r-t wrote:
       | So the six finger hands were just a foreshadowing?
        
       | Karellen wrote:
       | Is this going to be as good as when AI arrived in the world of
       | materials science?
       | 
       | https://www.404media.co/google-says-it-discovered-millions-o...
       | 
       | Or is it only just going to be as good at generating headlines?
        
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       (page generated 2024-04-23 23:01 UTC)