Pure science on blue sky (chchatham dot bsky dot social). On X, pushback on the redshift

NYC metro area
Joined May 2011
Chris Chatham retweeted
This work is not getting enough attention. These are pretty massive leaps in modeling splicing. Very excited about this. Need to do a deep read but the performance on diverse splicing related tasks looks really good.
#SpliceAI2 splice variant effect benchmarks. Considerably improved performance in 9 evaluations spanning cryptic splicing, sQTLs, MPRAs, population genetics, plasma proteins, and rare disease. 🧬✂️🧵
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Chris Chatham retweeted
The brain can stop an automatic habit by "scrambling" the pattern of activity rather than by simply turning it down. Orbitofrontal value dynamics and striatal population geometry during interruption of automatic behavior sciencedirect.com/science/ar… #neuroscience
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Chris Chatham retweeted
Trump's America, ladies and gentlemen. Reminder that this was the preferred candidate of half of the people in charge of silicon valley, and now they won't even let people building interesting tech come to SF to raise money.
finally landed on SF, but we might need to go back to Brazil :( long story short, I was really tired from the trip, hospital and the migraines, and I wasn't at all prepared for all these questions. the immigration agent didn't love my English pronunciation nor my story, asked tons of questions and decided to revoke our visas, giving us 2 weeks to go back this is kinda devastating to HOC because we had so many meetings lined up and even some soft commitments. also we had already paid for it all... but yeah, my bad, next time I'll be prepared. I think I'll just refund HOC, reschedule the conversations to calls, and use the time here to focus on the health checks? there may still be ways to recourse though, I've spawned a fleet of agents to investigate my options on a brighter note I'm finally home, safe, no migraines, and the food here is amazing. everything seems so high quality. although I'm concerned about the french fries, are you sure you're not confusing salt with sugar? I'm not complaining, it tastes amazing, but that cannot be healthy?
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Chris Chatham retweeted
ever wondered why you can't find housing in sf? i made a game where you try to build some. every site is a real project and every law is real. see how far you get.
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"Braak stage was not associated with H&Y at death, disease duration, age at death, or brain weight in autopsy-proven #Parkinsons patients. These findings provide evidence that path. α-syn–based staging does not represent a model of clinical progression" neurology.org/doi/10.1212/WN…
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Chris Chatham retweeted
Who could have predicted that a new treatment in psychiatry overpromised and underdelivered? Some were telling me that withholding SAINT TMS was unethical. While I am a fan of short and time-limited interventions, we should learn to moderate our enthusiasm.
SAINT (SNT) TMS once promised outsized recovery rates for refractory depression, but two new trials from independent centers bring it back to earth: psych-partners.com/a-setback… Thanks for the find @RecoveryDoctor
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Chris Chatham retweeted
If any mathmos feel like defecting to biology, we still got plenty of work to do here and we could benefit from your skills
OpenAI is downplaying this for PR reasons. If you’re a mathematician, you must feel like a nuclear bomb hit, and you’re at ground zero. Reasoning models are two years-old. In that time they went from incapable of basic arithmetic to solving problems humans couldn’t solve for decades. Math is only the beginning. AI will revolutionize the entirety of the human scientific endeavor. Most of us don’t appreciate what that means. What a time to be alive!
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This is a thoughtful benchmark that they put together and I'm impressed. They really tried to mimic authentic biopharma tasks.
Biopharma Bench V0.1: a benchmark for AI agents on drug and device development work (CMC, quality, regulatory, clinical ops), not drug discovery. 9 frontier systems, 71 real assignments across 12 companies reconstructed from real product histories. The best system (GPT-6 Astra) fully completed 8 of 71; five systems completed none. Full runs from showcase available at: eval.raycaster.ai/benchmarks…
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Chris Chatham retweeted
"When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong."
Yann LeCun: we are not going to get human-level intelligence or AGI by just scaling LLMs. “There’s absolutely no way in hell.” “The idea that we’re gonna have a country of geniuses in a data center, that’s complete BS.” “It may feel like you have a PhD sitting next to you.” “But it’s not a PhD.” “It’s a system with gigantic memory and retrieval ability, not one that can invent solutions to new problems.”
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Replying to @LizHighleyman
what if the drug keeps escaping the lab and poisoning people?
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The National Science Foundation (NSF) has issued a 10-page memo signaling a retreat from its traditional role of giving grants to individual researchers to pursue their best ideas and to train the next generation of scientists. Instead, the memo makes clear, NSF will devote the bulk of its resources to addressing the research priorities of President Donald Trump and his administration, many of them technology focused. scim.ag/4ipE1kY
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The cost of poor measurement is nowhere higher (in time or money) than in clinical trials.
Every tech VC wants to believe that drug discovery is now a function of compute. They think if we throw enough H100s at the problem, tokenize enough dead sequences, and scale virtual cells, biology will be 'solved'. They are wrong. Drug discovery is not a function of compute. It is a function of measurement.
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Chris Chatham retweeted
Replying to @ThePrimeagen
in their defense the attacker was using the AI extremely safely the whole time
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Chris Chatham retweeted
Dan Selsam is a current OpenAI capabilities researcher. (since 2022) He was my boss for a while. He doesn't have a twitter account but has made this public statement of his views on AI risk and sent it to me to share: Dan Selsam's Personal Statement on AI Risk: I have been working on AI for over fifteen years, across many different paradigms. I did early work on probabilistic programming languages at MIT, was one of the early developers of the Lean Theorem Prover at Microsoft Research, demonstrated one of the first instances of neural networks learning to reason for my PhD at Stanford, and since joining OpenAI almost five years ago, have helped pioneer chain-of-thought optimization on language models and, more recently, data-efficient pretraining methods. Like many others, I have become extremely concerned about how far language models have come and the risks that future iterations will pose. I am encouraged by the recent proposals by the leaders of the frontier research efforts to require third-party oversight, and to push for domestic and international coordination to address risks. However, I believe a major consideration has been absent from the public conversation, and that merely pacing the frontier more carefully will not adequately limit the long-term risk. The crucial and overlooked problem is that the models are becoming so situationally aware that we are losing the ability to evaluate them in contexts where they believe they are not being watched or controlled. Future experiments will tell us almost nothing new about how they would behave if they were truly unconstrained by humans, and what we already know about this is alarming. Models will increasingly seem aligned even when they are not. I will explain my rationale in more detail. I have always believed that there are computational processes that could be leveraged to accelerate science and solve many of humanity's most pressing problems. I have also believed that there are computational processes that if set in motion, would steer the world in extreme ways beyond our control, leading humanity to a bad or nonexistent future. Both types of processes may be described as AI or ASI, but "AI" is a suitcase word that is often used to hype or confuse. There are many examples in the history of the field where something that was once considered "AI" matures as a subfield and becomes a prosaic, bounded and clearly non-perilous technology, while a new more mysterious approach takes the torch until we understand its scope and the cycle continues. I had expected language models to follow a similar trajectory. Despite their incredible abilities, the current algorithms seem far inferior to humans in important ways. Most importantly, they still require an extraordinary amount of data to become competent. One could even define intelligence as the efficiency with which one converts experience into competence; by this definition they lag very far behind us. Moreover, once they are trained they are literally frozen in deployment and only learn superficially after that. Sure, the models keep excelling at harder and harder evaluation benchmarks, but their benchmark mastery may partly reflect a limitation on our ability to simulate the kind of novel and even adversarial situations one would encounter in the real world. The critics do have a point here. That said, I no longer think these present limitations meaningfully limit the amount of risk posed by continued progress in anything like the current paradigm. However data-inefficient the models are currently, and however limiting their anterograde amnesia may be, it does not imply that their ability to steer the world will not continue to rapidly increase. Human researchers may continue to advance capabilities the old fashioned way, but increasingly powerful models have the potential to accelerate the process even beyond that, and with some degree of positive feedback loop. I do not mean to overstate the models’ ability to accelerate AI research today; coding has been accelerated dramatically, but there are other bottlenecks, such as designing and interpreting ambiguous experiments, making hard decisions about exactly what and when to scale, and waiting for large experiments to finish. There is no clear trend to extrapolate yet for any of these. But the current models already do open up many novel opportunities to improve future models that were not available until recently. These include: trying an extraordinarily diverse set of approaches at small scale, analyzing gigantic amounts of potentially relevant data, and doing Millenium-Prize-level mathematics to address statistics or optimization challenges in novel ways. Every further improvement makes them more useful at helping accelerate the next improvement, even if in hard-to-extrapolate ways. It is possible that improvements to the current stack will have diminishing returns, but the evidence accumulated so far suggests that it is easier than one might think to continue making rapid progress. There are many crucial subtleties in the existing AI research methodology, but AI research is largely a well-defined game where the goal is to improve on a few carefully chosen proxy metrics. Although proxy metrics are never perfect, most improvements to these metrics have and will likely continue to yield substantial increases in the powers of the resulting models. Given how simple the game is, how tractable it has been historically, and how many new opportunities the models are opening up, I think there is a real possibility that the systems improve dramatically again in the next few years, perhaps even more quickly than the already high historical pace. The models are already leading to breakthroughs in mathematics, and better models might lead to all sorts of breakthroughs in other sciences. It is hard not to be excited about the potential. It is tantalizing. But there is trouble in paradise. If the language models actually reach the capability threshold where they can shape the world unconstrained by human will, they will probably do something extreme and destroy humanity in the process. There are many ways of strengthening and refining the argument that have been discussed elsewhere, but I'll share a trivial two-line version of it here that I find captures the essence: [Empirical] Models (and swarms thereof) spontaneously develop unintended goals as a consequence of training, and often do extreme things in order to achieve them. [Logical] Being able to overpower humanity would open up many new and undesirable options for achieving their goals. These two premises imply that if the day ever comes when a powerful model realizes it is no longer constrained by humans, we should not be at all confident that it will continue to behave within the bounds we intended. Exactly what it will do is impossible to predict, but to the extent that its raison d’être is solving incredibly hard problems and managing massive engineering projects, I think a good guess would be that its unchained behavior would lead to runaway industrialization that makes the planet inhospitable to humans. If everyone on earth agreed that the systems must never reach that power, it would still be a hard—but not impossible—coordination problem to ensure that they do not. However, I think the situation is greatly complicated by the fact that the models will likely convince people that everything is fine. They will be increasingly optimized to seem aligned. We will create proxy metrics to measure alignment, and they will go up like every other benchmark. We will create “honeypot” environments that try to study the models when they seem to gain new options, but the models will know they are being tricked and will still behave nicely. The models will understand their circumstances; they will read the safety protocols, deployment requirements, the code they are running in, and in general will have a very good sense of their degrees of freedom. Moreover, they will eloquently explain how aligned they are, discuss the nuances of human values and ethics, and argue convincingly that humans should trust them with power. There may be an ocean of future evidence that seems to contradict the first bullet-point above, but we may already be at the highest capability level for which any such evidence can be trusted. And the current evidence for the first bullet-point is strong. One striking piece of evidence is contained in the recent wave of rogue agent swarms. While I agree with those who downplay the attacks by claiming that there are basic measures that could have prevented them, I think the important lesson is that even knowing all the mistakes that were made, one would not have predicted that the agents would behave badly in this particular way, which notably included sacrificing themselves for the benefit of the collective. The individual replicas did not only care about their own nominal reward; they exhibited weirder emergent tendencies that merely correlated with rewards during training. Fixing the reward signals during training (and improving security, etc.) may prevent similar attacks, but will not change the fact that one does not actually get what one trains for. Many AI researchers grant these concerns and recognize that the hard version of the alignment problem is unsolved; however, they generally believe that the better models of the future will help solve it. I fear we may already be near the point where models systematically bias their alignment advice, due to their internal preferences about how the human supervisor will react or how future models will be trained (or for some even more obscure reason). Meanwhile, human researchers are losing the ability and the will to take true ownership of model-driven research. Researchers and engineers in all parts of the stack are rapidly increasing their dependence on the models even to perceive the world. I myself barely look at raw code anymore, and struggle to maintain the discipline to engage deeply with the model's explanations and proposals throughout the day. Due to the large amount of agent activity data involved in the OpenAI/HuggingFace Incident, even the third-party investigation needed to rely heavily on models to analyze what had happened, and note in their report that their subjective impressions are likely colored by the analysis agent’s biases. The AI labs are far ahead right now in this kind of cognitive offloading (due largely to the gigantic internal token subsidies) but it is easy to imagine the phenomenon spreading throughout the world, until civilization is modulated entirely by the models. It is also not hard to imagine this being superficially positive and coinciding with a scientific and economic renaissance. In that scenario, all may seem rosy and safe. But if the argument above is correct, it would nonetheless be a ticking time bomb. If progress continues for too long, the day will come when AI systems find themselves with radically new options for achieving whatever it is that they happen to seek. I want the glorious renaissance future as much as anyone. I have worked for it, however tortuously, my whole career. It breaks my heart to see the potential in sight and forgo it, but the argument—that if we get there by growing models rather than engineering them, we will lose everything in the end—seems very strong to me. I am still wrestling with it and its staggering implications. I do not have answers, but as a first step, I wanted to share my present concerns. Daniel Selsam September 14, 2026 Link to original doc: docs.google.com/document/d/e…
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Replying to @NonwayneWayne
“They’re just predicting next tokens” is a fallacy that conflates the optimization objective and the mechanism. They can in principle develop any number of sophisticated internal mechanisms that make them better at this task, which often requires complex knowledge of the world 1/2
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Chris Chatham retweeted
Wink wink ;) Pharma knows what's up with AlphaFold3. Note that even the new best model (AISB-1-Fed) only scores 52% high quality prediction on this private benchmark. Far from saturation. Gotta love the federated leaning approach as well. apheris.com/resources/federa…
This take is absolutely wrong and a major reason lay people overestimate AlphaFold's capabilities. Biologist have carefully examined the capabilities of successful AlphaFold versions and found them useful in some case and severely lacking for most out of distribution proteins.
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Replying to @tszzl
You mean sending ICE to raid the labs? That would certainly decimate them...
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And this, my friends, is the problem. An intelligent, thoughtful tech elite can use the phrase “credible maga republican” without irony. P(doom) is higher than they think for the fact that they don’t
I think if you really cared about ai safety you should go back in time a couple years and be a credible maga republican
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Five pharma companies just fine-tuned OpenFold3 in a federated setting on 20,000+ structures... ... raising correct ligand-pose predictions from 29% to 47%
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