Calvin McCarter (@CalvinMccarter) header
Calvin McCarter (@CalvinMccarter) profile picture

AI + bio | Views not always my own, but never more than my own | spicier takes and toddler photos @TrainOnTest | https://xitter.gq/t.co/KfBNuwu51j

Boston
Joined November 2018
Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)Photo by Calvin McCarter (@CalvinMccarter)
Calvin McCarter retweeted
we have improved the opendde inference process, allowing more efficient and effective co-folding, from 0.14 to 0.75 top1 success rate with inference guidance. this week, we will update our codebase with a short tech report for people to review. this new inference algorithm can be used in anthropic x adaptyv protein design challenge ❤
AI Drug Discovery Is Becoming a Bottleneck Trade I get excited when an industry starts going through a real regime change. AI drug discovery (“AIDD”) increasingly looks like one of those moments. Two things are happening: 1/ Upstream: the frontier AI labs are piling in. 2/ Downstream: The supply chain is clearly moving. Supply-chain checks suggest the upstream picks-and-shovels of discovery and early preclinical R&D are starting to feel the increase in experimental volume. DNA → protein → assays → sequencing → automation → preclinical testing Names across that stack include $TWST , @GenScript , $ILMN , $TXG , lab-automation vendors and CROs. $TWST expects triple-digit percentage growth in AI-enabled drug-discovery orders in FY26, and another year of triple-digit order growth in FY27. @GenScript's AIDD business doubled YoY in 1H26. Its current platform advertises industrial-scale validation of 4,000+ designs/day, with integrated sequence-to-data workflows. Our channel checks suggest the ramp is moving even faster: roughly 8,000 designs/day currently, with a path toward ~16,000/day by YE26. --- Why does AI drive more wet-lab demand? 1/ AI makes hypothesis generation almost free → way more shots on goal. The bottleneck is moving from expert-driven design to biological validation. 2/ AI models need continuous experimental feedback — and both good and bad data are useful. Traditionally, only the highest-conviction A+ candidates might get pushed into expensive validation. With AI, even the B/C candidates can be valuable because failed experiments generate training data. @GenScript has said its sequence-to-binding workflow can return data in 4–7 days, and that faster cycle times matter because AI models depend on continuous experimental feedback. @Anthropic is a clean example. @claudeai designed 1,320 protein binders. @adaptyvbio converted those digital sequences into DNA, expressed the proteins and tested binding. Only 354 actually bound. And the 966 failures are not wasted. They are useful negative labels: what does not express, what does not bind, what has poor affinity. Those results help train the next model iteration. 3/ Wet labs are no longer just making drugs. They are making training data. $TWST / @GenScript increasingly look like biological data foundries. $TWST explicitly talks about generating model-ready data from AI-designed sequences. In some workflows, the customer may care less about receiving the physical protein than about getting structured experimental results back into the model. Traditional drug discovery asks: “Does candidate X work?” AI drug discovery also asks: “What can this experiment teach the model?” --- TAM of AIDD If AI is simply a better R&D tool, the relevant spending pool is the $300–400B of annual global pharma R&D. If AI meaningfully increases the number of viable drug programs, the opportunity is larger because it expands downstream demand for DNA synthesis, protein production, assays, and preclinical work. Near term, we can also size demand from AI-company spending. If Anthropic reaches $80B of ARR in 2026 and spends just 1% on AIDD, that alone would imply ~$800M of annual investment. --- Trade setup This is a trade that could have long legs. It’s hard to really stop working until PhaseI/II results (2028+) It smells a lot like the bottleneck trade we just saw in semis: GPUs → HBM → networking → power/cooling. In biology, It basically follows the drug discovery process downstream: AI models → designs → DNA/protein → assays → preclinical capacity. After the upstream picks-and-shovels, animal testing could become the next bottleneck. Monkey prices are already near prior highs and CRO capacity is tight. AIDD pushing more candidates into preclinical development would only add demand. ?? But clinical trials are still the bottleneck? This is the biggest pushback I keep coming back to. No matter how fast discovery becomes, drugs still need to go through preclinical → Phase I → Phase II → Phase III → approval. You still need patients, time and capital. But that doesn’t mean the bottleneck trade won’t work. More viable candidates — especially with higher success rates — still means more demand throughout the development process. And who knows: clinical trials themselves may eventually be optimized by AI. ?? What breaks the trade? Near term, the picks-and-shovels trade breaks if experimental budgets stop growing, AI-generated designs don’t translate into useful wet-lab hits, or capacity catches up too quickly. Longer term, the thesis breaks if AI drugs look great in discovery / Phase I but fail at normal rates in Phase II/III. That is why Phase II matters so much. ?? Milestones Late 2026–2027: first Isomorphic-designed drugs enter human trials; more AI-native programs move into IND-enabling work / tox. 2028–2030: clinical trial results start telling us whether AI-designed drugs actually perform better than conventional drugs. Calling all the "bottleneck bros". :) @jukan05 @zephyr_z9 @aleabitoreddit @ParadisLabs +++ More comprehensive analysis: robonomics.substack.com/p/ai…
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Calvin McCarter retweeted
Short term yes CROs are gonna pump, long term there’s too much alpha in having a model that eats its own cooking. In house labs are going to be table stakes
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Calvin McCarter retweeted
Everyone working with AI should read this.
I've got a pretty clear picture now of where we're headed next year, when Fable-class models become ubiquitous and cheap, and every enterprise is flooded with hundreds of new Fable-class AI employees. Spoiler: They create a constitutional legal system. yegge.ai/essays/fences-not-s…
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Calvin McCarter retweeted
i think that i often think of the beautiful things that ai will enable us to have; for instance, today i was walking in the japanese tea garden in sf; and, there are many stone lanterns there, which are unlit, some in the middle of a pond. of course, the labor to light these would be too much right now, it is too hard to get a boat and go and light the lanterns; it would be significant labor at opening and closing; we could probably do this with drones, but the cost of a programmer, matching the programmer to the tea garden, etc… is prohibitive; just purely on a transaction cost basis but, ai will solve this; we will be able to have these beautiful things; claude could order all the drones and the candles and do the programming for them to do their circuits around the garden, and the administrator of the garden would only need to say yes, inspect it a few times, look at the candles and give it the go ahead this is the smallest example of what is possible with distributed intelligence; there are so many things in the world that are prohibitive because of the cost of specialized labor and coordination and planning costs and ai can set these things free
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Upcoming seminar: Tuesday, July 7, 2026, at 4:00 PM Eastern Time. We’re excited to welcome Calvin McCarter, Senior Machine Learning Scientist at BigHat Biosciences, who will present “How to Make the Most of Your Masked Language Model for Protein Engineering.”
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Calvin McCarter retweeted
We are all Emil now
🤖 Made with AI
mythos will be bad ON PURPOSE on ai "frontier llm research" tasks, this is very very sad for the research community also the fact that this is un purpose not visible to the user is crazy
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Overheard in Boston: Wokeness is cancelled, so we get to say "happy CHINESE new year, not happy LUNAR new year" again!
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Calvin McCarter retweeted
Finally got around to putting our new paper on visual interpretability of LMMs up on arXiv! The basic idea of the paper is very simple -- (1) use a VLM like CLIP to label arbitrarily large numbers of concept directions in LMM latent space, (2) use gradients to measure
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Calvin McCarter retweeted
the reason spaced repetition isn't a thing for deep learning is that we don't have learned optimizers. if we did, and used spaced repetition, then the optimizer might learn to detect spaced repetition and give greater priority to those samples.
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Calvin McCarter retweeted
this suggests that the human learning update algorithm is an evolutionarily-learned optimizer, and that it meta-learned via evolution to prioritize spaced repetition-like data. so anki spaced repetition is kinda like supernormal stimuli for that algorithm.
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Calvin McCarter retweeted
Replying to @tszzl
You'll code nothing and be happy
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Just take a screenshot bro.
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Calvin McCarter retweeted
Do you need predicted 3D protein structures for antibody optimization using BayesOpt? We examine this in a new paper, which will be presented at AI4Science & SPIGM @NeurIPSConf and MLSB. (TLDR: sequence-only BayesOpt approaches can match methods incorporating structure!)🧵(1/5)
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Calvin McCarter retweeted
Replying to @ChrisMurphyCT
You're being played by people who want regulatory capture. They are scaring everyone with dubious studies so that open source models are regulated out of existence.
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Replying to @tszzl
this is also why preschool to the universe should be like Montessori in the limit, a guide through the wisdom of the ancestral learning environment, up to the entire world xitter.gq/DanielleFong/status/19…
the problem isn't the dopamine, that problem is the static, nearly passive environment from which it comes that short circuits the learning environment of our ancestral memory. montessori is the limit is a park - learning lab that eventually extends to the entire universe
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Calvin McCarter retweeted
Replying to @CalvinMccarter
Only if your utility is dumb, see Nevada as example of how it can help. Datacenters are not that variable in power + demand response means it's a great user to grid assuming they handle transients properly.
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Calvin McCarter retweeted
Replying to @_Mira___Mira_
Yes, we have done that! openai.com/index/nonlinear-c… 3 Linear layers is all you need for 99% accuracy on MNist
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Making AI useful in the lab: the missing math of active learning A call for greater first-principles theory to power lab-in-the-loop science with @BlackHC and @paulmorio
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Unmasking Trees for Tabular Data Calvin McCarter. Action editor: Jes Frellsen. openreview.net/forum?id=0Axb… #generative #imputation #tabpfn
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