why aren't all 22 resolved? a statement only gets an assessment when the public
record can support or contradict it. opinions and what-ifs never can, and 0 checkable
ones are still open, waiting for their date. predictions held up or didn't;
assertions are supported or contradicted. on every card:
▮▮▮▮▮ certainty ·
▮▮▮▮▮ debate potential. speakers are clickable
Assertion Supported
ESMC model search generates novel antibodies achieving therapeutic-grade binding affinity levels
“What we're able to see is that, you know, you can search ESMC and you can actually find antibodies that are reaching the level of affinity that are, I should say, are really at the level of affinity that is needed for therapeutic function and activity.”
Assertion Supported
Rives: ESMC is state of the art among open models for multimer prediction
“Yeah, I mean, I think we're state of the art for open models.”
Prediction Not checkable as stated
AI cell simulations will enable parallel reasoning across millions of biological hypotheses
“We're gonna have increasingly capable and accurate digital representations of molecules, genomes, cells, ultimately physiology. That's where you want to get. We're gonna have to go up that, that complexity scale, the levels of biological complexity that requir…”
Insight
Rives: Curing disease requires personalized computational models, not conventional pills
“What is, you know, what is the cure to disease look like, right? It's not a pill, right? It's not a medicine in the conventional sense. You know, it's going to have to be a system that is capable of modeling and understanding, you know, the underlying physiolo…”
Opinion
Rives: Current Virtual Cell Models Cannot Predict Novel Interventions
“I think with, you know, kind of the current generation of models that are being called virtual cells, they are good representations of the underlying data, but, you know, they have a very limited ability to predict what will happen when you make a novel interv…”
Assertion Not checkable as stated
Scaling protein models by orders of magnitude unlocks emergent biological capabilities
“So our team has really explored that idea over a number of different years, and we've really kind of, I think, seen the scaling curve and really seen as we have increased models by an order of magnitude kind of in each generation that, you know, there's this e…”
Assertion Supported
Sparse autoencoders found a single learned feature for nucleophilic elbows in ESMC
“You know, what we found basically is that the model has a kind of a single feature for this nucleophilic elbow and is activating across these like very evolutionarily diverse families, you know, really completely different structural topologies, proteins that …”
Assertion Supported
Incorporating metagenomic training data eliminated diminishing returns in ESMC protein foundation models
“And then, you know, what we saw basically is, is, is there are no longer diminishing returns to scale. So that's really saying that ESM two was kind of data limited rather than compute limited for ESMC.”
Assertion Supported
Rives: ESMC Has Been Used to Successfully Design scFv Antibodies
“We've been able to use this to actually now go and design many protein binders, but I think sort of most excitingly, we've been able to use this to actually design antibodies, SCFVs, and we're seeing really, I think, exciting success rates and a small number o…”
Insight
Rives: Sequence diversity teaches models structure while small variations teach function
“Having a vast diversity of sequences across a wide range of protein families is, you know, really critical for the emergence of this kind of structure Prediction capability, because I think kind of large diversity is what trains the model to understand, to dev…”
Assertion Supported
Rives: Meta FAIR trained the first protein transformer language model
“And so my team, when we were at MetaFair, trained really the first transformer language model for protein biology.”
Assertion Supported
Biohub predicted 3D structures for 1.1 billion proteins from global sequence databases
“So we put together kind of all the world's largest protein sequence databases. And so that kind of amounts to 6.8 billion non-redundant proteins, and then we've resolved predicted structures for 1.1 billion of those, and we've also computed features across all…”
Insight
Rives: Amino acid sequence patterns allow protein language models to learn biology
“The contexts in which an amino acid can occur are really determined by, you know, the structure, the function of the protein, its biological roles, you know, these I mean, very complex phenomenon both the intrinsic biology of the protein and its relation to al…”
Assertion Supported
Rives: ESMC Added Billions of Metagenomic Sequences Beyond UniRef
“ESM-II is trained on Uniref. And for ESMC, we added metagenomics. So we added billions more sequences to the training data.”
Assertion Supported
Feng Zhang's laboratory used the ESM atlas to discover novel gene editors
“Actually, the first version of the ESM atlas was used by Fang Zhang's group to find A new gene editing system.”
Assertion Supported
Rives: ESMFold 2 yields atomic resolution predictions in seconds without MSAs
“So the other thing about ESM fold two is a really fast model because it doesn't require the multiple sequence alignment. So You know, you can do inference kind of, you know, directly from the sequence it takes seconds, you know, you can get an atomic resolutio…”
Disclosure
CZ Biohub commits $500M to scale biological data creation and technology development
“We announced a few weeks ago, the virtual biology initiative we basically said, you know, we're gonna invest four hundred million internally in data creation and development of technology to scale data generation to be able to increase the number of modalities…”
Prediction Not checkable as stated
Rives: Existing Tech Can Scale Biological Data 10x–100x Before Hitting Limits
“I think with current technology, you know, we can definitely kind of get, get data, 10 X to a hundred X where it is today with like relatively reasonable investments, you know, but then to get another 10 X or more in there, that's going to require, require a l…”
Disclosure
CZ Biohub is open-sourcing the ESMC protein foundation model under MIT license
“At the time that this podcast comes out, we will have announced ESMC and this world model for protein biology. It's gonna be open source. It's gonna be MIT licensed, and we want people to use it.”
Opinion
Rives states he believes in scaling laws for biology
“Well, I'll take that. I believe in scaling laws, so”
Assertion Supported
Rives: The ESMC family includes 300M, 600M, and 6B parameter models
“So there's actually three models in that family. There's a three hundred million parameter model, a six hundred million. Parameter model and a six billion parameter model.”
Disclosure
Biohub is building high-contrast cryo-electron tomography for atomic cell imaging
“At Biohub, I mean, the other thing that we're thinking about is can we actually experimentally resolve this? And so one of the things that we are building is cryo-electron tomography, and we're really building systems that can greatly increase the contrast Whe…”