
Chris J. Maddison retweeted
Simulations need starting values.
We don't know enough to give even infinite compute the information to do such a simulation.
It is literally impossible at this point in time to gather anything close to complete data about the current state of a single cell.
If you had an exponential amount of compute you could solve simulate biology exactly and wouldn't need to run any experiments.
Some of you will think "of course, but that's an unrealistic assumption" and others will think "no, you need experiments even with that much compute. That's just How It's Done".
You would of course need evaluations once you have a solution, but you don't in principle need experiments to find it: Experiments are a way to save compute, dating from a time when it was much more expensive.
And I think the presentation is exponential but real systems aren't irreducibly exponential. AlphaFold worked, after all.
Chris J. Maddison retweeted
Our new work using virus-specific T cells as biosensors in Long COVID. These data point to viral persistence detected by T cells and some level of T cell exhaustion. Excellent work by @markmpainter biorxiv.org/content/10.64898…
Chris J. Maddison retweeted
✨Introducing Prompteina: all-atom protein design directly from natural language✨
- Control diverse protein properties through a single text prompt
- Higher predicted binding confidence than baselines
- First experimentally validated de novo binders reported for GM2A
🧵
Chris J. Maddison retweeted
Over 400 researchers and I have signed this open letter calling for the AI and security communities to come together to improve alignment and containment approaches in order to protect our critical infrastructure and digital systems.
ai-security-letter.org/
Chris J. Maddison retweeted
Over 400 academics in 30+ countries signed our open letter calling for immediate changes in AI development and deployment practices to ensure that cybersecurity incidents do not continue to occur, as future incidents will be far more damaging to our critical infrastructure.
Chris J. Maddison retweeted
Deep learning is often taught as a sanitized collection of facts and math. But work at the frontier of AI is messy and empirical.
Our new class, Deep Learning Alchemy, aims to teach the art and science of deep learning in the hands-on spirit of Language Modeling From Scratch.
Students build intuition by running experiments on small LMs, then test it through prediction quizzes: given an unseen code diff, can you predict what happens?
deep-learning-alchemy.github…
My co-instructor @kothasuhas and I think there's significant demand for classes that treat students as serious learners who want to be assessed for what they’ve learned, and so we're trying a new exam-heavy approach to the class (7 exams, 85% of the grade, with the remaining 15% in-person discussion assessments).
We’ve designed the class so students can use AI agents to run their experiments and do their assignment, but they then have to demonstrate that mastery on exams without access to the assignment, and any partial credit on the exam has to come through citations to the assignment, incentivizing them to know what’s in their write-up.
The same assignments and quizzes are public for anyone to try (lecture recordings will be released through @StanfordOnline with some delay). We have some very fun assignments and quizzes covering both classic topics (like NQM, run-to-run stochasticity, and scaling laws) and new and timely topics like muP or hyperball. Made by some real experts like @TristanThrush and @wen_kaiyue
Try some quizzes below!
Isomorphic Labs, an AI-powered drug discovery startup spun out of Alphabet’s Google DeepMind, is in early talks to raise new funds at a valuation of at least $40 billion, according to people familiar with the effort. bloomberg.com/news/articles/…
Chris J. Maddison retweeted
True and these medicines need to be extremely SAFE!
My bet that medicines will be some of the biggest consumer products of the next 20 years hinges on two questions:
1. Is the demand there?
Emphatically yes.
Tirzepatide, the molecule behind Mounjaro and Zepbound, already generates more in revenue than Netflix.
Equally striking: more than half of these prescriptions are self-pay. People are spending their own money on medicines that meaningfully improve their lives.
Even a product as good as tirzepatide leaves plenty of room for improvement. And weight loss and diabetes are just one part of the opportunity. Better sleep. Less pain. Fuller hair. Clearer skin. Better treatments for cancer and cardiovascular disease. The unmet needs are enormous.
The demand question is relatively easy—the harder question is below.
2. Will we be able to build these medicines?
My bet is yes. But this is where most of the uncertainty lies.
Three reasons I’m optimistic:
- Drug development is becoming like software. Increasingly, a lot of the research & analysis that is required at all steps of drug development can be done via LLMs. As a result, these steps can be composed within systems and automated. This allows small AI-native teams to do in days & weeks what required dozens of PhDs months to do. With billions going into AI × biology, I expect this trend to only accelerate.
- Our biological toolkit is expanding. CRISPR and base editing. siRNA and mRNA. Bi/tri-specific antibodies, antibody-drug conjugates and targeted protein degradation. CAR-T and emerging in vivo CAR-T approaches. We have more ways to intervene in biology. Better delivery technologies and half-life extension can help medicines reach the right tissues and work longer between doses. Together, these advances expand the range of medicines we can build.
- I have a positive regulatory bias. While regulation is always tough to predict, some of the recent steps from the FDA have been positive. FDA is developing clearer pathways for historical patient data and Bayesian methods in trials, while advancing validated alternatives to animal testing. These changes could reduce development time and cost. As unmet needs continue to grow, I expect more pressure on FDA to keep modernizing.
Twenty years is a long time for these improvements to compound.
Why I could be wrong:
- Biology takes time. Some steps in drug development are inherently incompressible. For example, establishing long-term safety and clinical benefit still requires observing people over time.
- Biology is hard to predict. Compelling mechanisms can still fail in large trials. Last month, Novartis’s long-awaited Lp(a)HORIZON trial showed that pelacarsen lowered Lp(a) but failed to demonstrate a statistically significant reduction in cardiovascular events. This contributed to a selloff that wiped roughly $30B off Novartis’s market value.
These constraints are real. But teams that combine scientific rigor with commercial discipline can bring great medicines to market.
Many of the biggest improvements we can still make to people’s lives are biological. Medicines can deliver them.
What’s a better consumer product than that?
Chris J. Maddison retweeted
Congratulations to @berkeley_ai faculty @irenetrampoline and @berkeley_ai alumni @BachFrancis @andrea_bajcsy @dan_fried @natolambert Juan Carlos Perdomo who have been named @schmidtsciences 2026 AI2050 Early Career Fellows.
eecs.berkeley.edu/news/irene…?
Chris J. Maddison retweeted
🚨 [Token][ization] Paper Alert 🚨
Tokenization is a wildly understudied area of language modeling despite it having effects across all of NLP. Over the past ~8 months, 32 (!) tokenizer researchers put together the most comprehensive survey of the field. Check it out!
Chris J. Maddison retweeted
Congratulations to @cjmaddison, who has been named a 2026 #AI2050 Early Career Fellow by @schmidtsciences. His project will develop new AI methods that help researchers learn from limited scientific data in settings like drug discovery. uoft.me/cID

ALT Graphic featuring a headshot of Chris Maddison centred on a blue-green gradient background with a circuit-board pattern. Large white text at the top reads “Chris Maddison.” Beneath the portrait is “University of Toronto.” The bottom left corner displays the “AI2050 2026 Fellows” logo, and the bottom right corner displays the Schmidt Sciences logo.
I am honoured to be joining the @schmidtsciences AI2050 fellowship this year. I owe this recognition to the people who I work with every day, most importantly my amazing students. This support will enable our research, and I am extremely grateful for it.
Today, Schmidt Sciences is excited to announce 28 new AI2050 Fellows tackling the defining AI challenges of our time, from understanding its risks to expanding what it can help us discover.
schmidtsciences.org/ai2050-f…
Chris J. Maddison retweeted
Today, Schmidt Sciences is excited to announce 28 new AI2050 Fellows tackling the defining AI challenges of our time, from understanding its risks to expanding what it can help us discover.
schmidtsciences.org/ai2050-f…
Extremely inspiring and amazing team! Can't wait to see more from @OrtetAI.
i was diagnosed with thyroid cancer many years ago purely by chance, because i had to get blood work for my US green card application (thank you, USCIS!). i was in my mid-30’s and was reasonably healthy (or so i believed.) this was shocking and totally unpredictable news to me. thanks to the amazing team of clinicians at NYU Langone, i successfully went through a total thyroidectomy followed by radioactive iodine therapy. but, it was truly the most uncertain and confusing period of my life.
this is when i first realized that no one can opt out of healthcare. being sick isn’t what you choose to or choose not to. it is something that unpredictably happens to all of us at some point for one reason or another. this is why it is a healthcare system that we collectively build and use to support each other at the society level. because it must support everyone, the complexity of creating, maintaining and improving this system is a Herculean effort that calls for all the help in the world.
today, i am announcing @OrtetAI together with my dear co-founders, @keunwoochoi, @HenriDwyer, @elmanmansimov, @causalclaudia and Jeff, to lend our support to improving the health of each and every one of us. Ortet’s goal is to create a technological foundation that will enable health systems to deliver predictably better care to each and every patient. this will only be possible by working closely with all stakeholders in the broader ecosystem, which is enabled in part by Ortet’s close partnership with Thoreau.
Ortet is taking the very first step of a long journey ahead, and at the end of this journey, i strongly believe we would be able to say that Ortet had contributed to building better, more predictable healthcare and thus to improving health of each and every one of us.
see ortet.ai/ for more!
Chris J. Maddison retweeted
🚨 New paper: Introducing MIND (Monge Inception Distance)
Everyone agrees that FID is broken, requires too many samples, slowing down evals.
MIND requires 10x fewer samples, is more robust, faster to compute.
Our new drop-in replacement for evaluating generative models. 🧵👇
Chris J. Maddison retweeted
Concentration of power in a few labs is the biggest risk in AI in my opinion
I’m very concerned that during RSI, labs will just stop externally deploying their models.
Which means they'll be going full steam ahead on the most dangerous use case of these models (recursive self-improvement), while the public remains in the dark about the nature of capabilities and the state of alignment.
And we end up on a path towards tremendous concentration of power.
Chris J. Maddison retweeted
Last month I wrote about how we can build a positive and safe future for everyone: meta.com/thefutureisforevery…
Every lab has the responsibility and incentive to move at the pace required to train its models safely, and the ability to take its own actions to ensure that happens.
The reality is:
- People won't want to use agents that are misaligned with them and that don't do what they ask, so labs have a strong natural incentive to make their models more aligned.
There is a lot of debate about slowing progress on capabilities until alignment catches up. My view is that trust and alignment are quickly becoming the most important capabilities that will differentiate agents and models. Any lab that doesn't focus on alignment will fall behind.
- Labs face significant liability if their models cause harm, so they have a strong incentive to prevent this as well.
Meta delayed shipping Muse for several months to focus on safety and security. We didn't call for everyone else to do this before we would. We just did it as part of our day-to-day work because it was clearly the right thing for people and for us. I'm proud of the security foundations we've built.
- Engaging independent evaluators and advisors is industry best practice. MSL already does this today in several areas because it helps produce better work. Other labs can just do this too. In general, it would be helpful for there to be a larger and more diverse ecosystem of evaluators.
- Committing the significant majority of compute towards serving people rather than racing towards recursive self-improvement is one of the best ways to ensure we develop this technology safely. Meta has made this commitment and other labs can do this as well.
I believe the key to building a positive future for everyone is maintaining the right balance of power. This is within our power to do.
Chris J. Maddison 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…
SITUATION DETECTED: Nvidia, Palantir, and Booz Allen Hamilton are restricting or eliminating the use of Anthropic and OpenAI models in some cases due to rising corporate data retention and intellectual property concerns, per The Information.
Chris J. Maddison retweeted
A more serious take on what is happening here. I am in an airport lounge so have some time.
Enterprises have made an uneasy truce with frontier labs over last few years: strict contracts that ban training on corporate data in exchange for letting employees use APIs.
The problem? Labs don't need to train on your raw data to copy IP.
Exclusive: Palantir, Nvidia and Booz Allen Hamilton are restricting Anthropic’s Fable model for sensitive work over concerns about its data-retention policies.
Some customers are demanding irrevocable zero-data-retention guarantees before putting proprietary information into the model.
Full story: thein.fo/4dekujW





























