The original article from @PatRubenFitz is fascinating but Sam's additional claim that iron caused the Late Bronze Age Collapse just doesn't line up. The collapse begins around 1200 BC and at that time, there was very little production of iron even though early iron smelters did exist. The iron that was traded was hematite, an iron that forms in meteors. A couple years back I wrote all about iron in the Late Bronze Age in a piece titled "King Tut's meteorite dagger: A weapon from the heavens" Link: exformation.williamrinehart.…. As I explained: "Tut’s blade is truly a rare piece because the total catalog of Bronze Age irons is so limited. Nearly every piece of Bronze Age Iron is made from meteorite. Axes from Syria and China dating back to about 1400 BC, a Syrian pendant from 2300 BC, a Turkish dagger from 2500 BC, and beads from Gerzeh, Egypt from 3200 BC all have levels of nickel and cobalt that line up with meteorites. Other than this blade, the Ugarit axe from Syria is probably the most well-known Bronze Age iron." The most comprehensive piece I read on the grand sweep of this history is Nathaniel L. Erb-Satullo's "The Innovation and Adoption of Iron in the Ancient Near East" Link: link.springer.com/article/10…. This piece really is required reading. It dispelled my initial thinking that the Collapse caused iron to be adopted. Erb-Satullo frames this as a push model. It is intuitive. Bronze requires tin, which was mined in only some select places including Cornwall, Brittany, and Cyprus. When the large civilizations collapse, those trading routes can no longer be maintained and so iron is adopted instead. But bronze production patterns don't show a clear collapse around this time period. The Cypriot copper industry seems to have expanded. Instead, I think there's better evidence for a pull model where political reorganization made iron attractive. Smaller decentralized polities exploited local iron rather than relying on extended copper and tin trading networks. As I wrote in that King Tut piece, "The significance of minerals in the study of history and political power cannot be overstated. Minerals have shaped human societies and political power in countless ways, from the use of copper and iron in ancient times to oil, rare earths, and silica of today."

I've been experimenting with BindCraft 2 and h/t @aaronmring it turns out that consumer GPUs on e.g. vast.ai can produce trajectories for really low cost! 2c/traj is incredible @MartinPacesa and his collaborators really optimized the hell out of this thing

Dark Forest era for math & theoretical science?

I love evals that help me learn more about a domain I’m already interested in

We are thankful to have participated in developing what we believe is the best therapy in multiple myeloma. Thank you to the brilliant investigators. The biggest thanks goes to the patients who took a huge risk participating in a phase 1 clinical trial. nejm.org/doi/full/10.1056/NE…

Happy Friday! Iʼve created a game for you to play! Will AI cure all diseases in 10 years? Inspired by bottlenecks discourse, I created a game to help build your intuitions. Play it here: game.clinicaltrialsabundance… Naturally, it’s bottle-themed with bubbles and there are leaderboards too.

I find it instructive to look at how FDA-approved cancer medicines behaved in preclinical studies - Clinically effective therapies usually *shrink* tumors in vivo, for a long time, at a modest dose, not just slow growth by a few days

t-cell killing cancer cells is so metal

Trying to build a FRO-like entity inside a university is tough! But people within the bureaucracy mostly want to help, even if what we’re doing is unusual wrt pace/assumptions; pieces slowly coming together, one form/waiver/ticket submission/zoom meeting at a time.

I had not realised before that the Bronze Age Collapse was literally *caused* by iron. Bronze age powers like the Egyptians, Hittites and Babylonians used bronze weapons, made by combining copper and tin. Tin was so scarce that only the richest and most powerful groups could access it and the bronze weapons it allowed. (Tin was so rare that it was being transported from Cornwall to the Middle East more than 1000 years BC.) The scarcity of tin gave these empires a near-monopoly on violence. Iron weapons are not actually any better than bronze ones – they're not stronger or easier to work with, as I'd assumed. They're just much, much easier to mass produce once you have bloomeries, which are the first furnaces that were hot enough to melt iron in a way that made them useable for weapons. Bloomeries meant that iron ore, which was widespread, could be used to make weapons anywhere. That led to warlords, bandits and city-states rising in a massive decentralization of military power, which the Bronze Age empires were unable to resist. After the invention of the bloomery, skeletons show a measurable increase in weapon-inflicted injuries. 'Destruction layers' with bones and signs of burning have been found from this time at archaeological sites including Troy. Ancient writers – including Herodotus, Ovid, and the writers of the Old Testament – believed the invention of iron had unleashed a new age of violence. New at Works in Progress, WEAPONS OF MASS DECENTRALIZATION: how iron itself brought about the Bronze Age Collapse. And what technologies could do the same today? worksinprogress.co/issue/wea…

Despite all the recent backlash against ASOs (due to a few bad trial outcomes), they still show they are a great class with the success of Ionis's Ulefnersen for FUS-ALS when Novartis mAb VHB937 failed

Ya gotta run the experiments, guys. All the inference in the world means nothin without validation. I know this is a foreign concept to Ai ppl but the living world cant be decoupled from the material reality it exists in; much of the parameters of said world await description...

you should start a biology research institution going after your own personal millennium problem. there has literally never been a better time

I am towards the end of writing an article about Eli Lilly and its rise and would like to interview some more people about the way pharma generally operates and also Lilly specially and potentially get quotes from them. Would really appreciate if anyone could offer to do it!

I would like to write a reported piece on orexins. Is there anyone who'd like to talk to me about their effects/ history etc?

Very excited for BindCraft 2! It's incredible to me that it feels like binder design took off like crazy over the past 18 mo, but BindCraft came out Oct 2024, and it's somehow still competitive with the best (see the Ant paper). Also a testament to the strength of AF2!

If anyone wants to work with me on something, I’ll probably be going after proteins to bind / destroy regulatory proteins related to biofilm formation and signaling like: SinR / AbrB / BrpA / BatR / CsrA/RsmA / c-di-GMP Effector Protein / OmpR/EnvZ system / FleR/FleS system / LuxS / Autoinducer-2 (AI-2) Dual goal seeking both therapeutic + industrial biofilm-busting applications

3. Direct data: Measuring biological and clinical states closest to what matters 🔬 Biology has spent much of its history measuring what was easy or cheap to measure. For instance: measuring individual cell data over human clinical data, or RNA expression rather than proteins. These proxies have been enormously useful, but they can also become detached from the goals of understanding biology, and of preventing and treating disease. In cases like this, we want to give researchers the resources they need to assemble datasets that measure what matters most. It may also be the case that the necessary instruments to measure “biological truth” do not yet exist, or are prohibitively expensive to use at scale. Within this program, we hope to support both initiatives – new data, and new tools. For example, our grant to @UNC to establish the Initiative for Generative Immunotherapy will allow the team at UNC Lineberger and UNC Health to produce the human-grounded data necessary to improve the next generation of cancer vaccines. That means measuring tumor cells’ surface proteins directly, as well as patients’ T cell responses, rather than “only” sequencing the tumor. This data is expensive to create; by doing it comprehensively this time, and making the results open, we hope all future cancer vaccine efforts will be able to benefit. In particular, if this project is successful, future vaccine candidates will be able to enter human dosing with a stronger set of targets. That should improve their chances of working, and increase what can be learned when they do not.