Ryan Spangler (@RySpangler) header
Ryan Spangler (@RySpangler) profile picture

Biotech Enthusiast 🧪 | Hobby Jogger šŸƒ| Investor/Trader šŸ“ˆ. Previously @broadInstitute and @NIH. Opinions are my own, not investment advice.

Boston, MA
Joined August 2018
Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)Photo by Ryan Spangler (@RySpangler)
Ryan Spangler retweeted
New Yamanaka preprint suggests rejuvenation by partial reprogramming must be optimized one cell lineage at a time. They investigate the key question of whether cells can become biologically younger, then recover their identity and function, while still maintaining the rejuvenation effect. After the reprogramming was done, 3 human cell types took on quite different trajectories: -Endothelial cells recovered their identity, retained a younger DNA methylation age and improved vascular function. -T cells recovered only after shallow reprogramming but showed enhanced effector function. -Fibroblasts retained a younger DNA methylation age but did not fully recover their proliferative capacity. The authors' conclusion: "Partial reprogramming involves a lineage-specific tradeoff between rejuvenation and recovery that must be optimized one lineage at a time." biorxiv.org/content/10.64898…
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Ryan Spangler retweeted
Replying to @FischerKing64
Longevity is coming
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Ryan Spangler retweeted
It's Halloween. Here's a trick-or-treat "thought experiment" for Anthropic (or OpenAI) going big into the Life Sciences. Probably more trick, than treat, but here goes... Both have made making medicines a top priority, as described in Anthropic's S1. Ā Right now they are taking some ā€œsmallā€ bets in the space (~0.1% of expected market cap's). Ā These are welcome moves and we are hopeful for more engagement in #biotech in general from the frontier lab companies. But if you are a $2T public company (as they are likely to be post-IPO), how could you achieve scale in this life science domain? Ā What’s the best way for maximum impact on bringing drugs to patients? [assuming that's the goal for their efforts in the life science] I’d argue it's buying a large Pharma company and then radically changing the operating model to put compute and integration in the center. Sort of like retrofitting a big Pharma R&D enterprise into a @NimbusTx model on steroids with compute and tech integration in the center, intercolated with deep biology and drug hunting capabilities, with operational execution on the periphery (impt, but not the driver). Own the learning loops, compress the DMTA cycle across a huge portfolio. Nucleate and empower teams around great potential medicines in a decentralized R&D model... Let me get vaguely specific, for illustrative purposes. Anthropic could buy $BMY for less than 10% of its market cap, an all-stock deal. BMS has about 30,000 people. Ā Trim commercial (a distraction to the radical change mission) by selling the long list of tail products (top 5 products are 70% of revenues). Then apply frontier AI models to the business across the board - commercial, manufacturing, and R&D. Tons of data sits in these silos. With data, figure out where the bloat is in the corporate bureaucracy and remove it. Be especially aggressive on scaling back G&A and the lawyers, replacing headcount in those functions with AI-enablement. Ā In the business functions, allow change-makers to focus on operational efficiency. In R&D, BMS has about 3000 scientists/clinicians and operators on their R&D team. Ā Keep or even grow this group - its where the magic has to start. BMS has a legacy of great R&D advances and has tons of historical data. Ā Frankly, they probably have some of the deepest datasets on mAb discovery (Mederex mouse one of the most prolific mAb platforms ever), induced proximity (CelMod and related datasets are without peer), cell therapy (Juno was a pioneer with one of largest CART datasets), radiopharma (more recently), and so much more. Deeply mine these datasets. Take all the "me-too" R&D spend on crowded targets and dial it out of the portfolio... Ā Refocus all that energy on building deep biology datasets to complement the historical modality data. Invest in deep cell and tissue profiling, all the ā€˜omics, at scale and in an integrated way. Ā Put AI into the center of the operational workflow as an enabling tool for drug hunters, not replacing them. Work on fewer projects as a whole, but focus on ā€œholy grailā€ drug targets and first-in-class/first-in-modality programs aiming for step-changes in treatment. And let AI operational efficiency compress clinical timelines as much as possible (10-20%). Unleash teams of drug hunters with AI-powered R&D at scale on any/all therapeutic areas, not restricted to where commercial wants you to focus. Ā A true science-first enterprise at scale. Ā ā€œA great medicine makes a commercial franchise, a commercial franchise doesn’t make great medicinesā€ rings true to me here. Commercial voices, I'm told, dominate at BMS, even back in R&D. Maybe that's not optimal? This would be a radical overhaul of a large R&D-intensive company. Ā Give the experiment 5-7 years to alter the vector of R&D output. Ā Long enough to see discovery-led changes percolate into early development and clinical PoC... This kind of ongoing R&D investment would be tiny fraction of Anthropic’s revenues during that period, offset in part by the profits from the big commercial brands. Ā A rounding error for them, but if it worked, this would fundamentally alter the industry’s trajectory. Probably can’t be done - changing large legacy groups is hard - but seems like the only near-term way to truly test ā€œAI at scale in drug R&Dā€ is thru something audacious like this, rather than just thru small (and beautiful) case studies of program-focused biotech … With $5T+ of anticipated market cap between the handful of frontier lab companies, this seems like a relatively small bet on a big prize. And, lastly, make @Prof_Oak_ head of the BMS business unit of $ANT. Trick or treat? Boo!!
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Ryan Spangler retweeted
SITUATION DETECTED: Prime Intellect is releasing Prime Agent, a self-improving harness for coding and long-running autonomous tasks. The team reports 95.5% on ARC-AGI-3, above the human baseline, and says the gain is not benchmark-specific.
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Ryan Spangler retweeted
Cape Verde btw
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Ryan Spangler retweeted
Got a chance to kick-it (pun intended ), with Nikki Hiltz ahead of Pre. Feeling confident they will get the American Record in the Mile on July 4th Check it out: youtu.be/7yM87TGBAmQ?is=BM5t…
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Ryan Spangler retweeted
I’m so excited to share this update on @Conception – We’ve generated the first early human eggs derived from stem cells. This is a big deal -- the potential to redefine fertility is real.
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just look at the timeline chad Midjourney just pivoted into medical hardware a full body scanner that uses sound waves and a pool of water to map your entire body in 60 seconds. no radiation. no MRI tube. no $1,000s bill could you imagine, an image generation company built this before most hospitals modernized their imaging that should tell you everything about what the future of medicine looks like turns out the companies with AI infrastructure and capital are now better positioned to build healthcare hardware than healthcare companies are biology just became the most interesting vertical for every serious AI lab on earth simply can't be bearish on biotech anymore bio/acc
Announcing a new division of Midjourney called "Midjourney Medical"
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Ryan Spangler retweeted
Big progress vs cancer, folks. The kind of event curves from randomized trials that we've not seen before for a couple of the most deadly cancers. Congrats to the oncology research community for getting these trial done. #ASCO26, @ASCO
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Ryan Spangler retweeted
RAS finally getting drugged is one of the great stories in modern biology, and almost nobody outside oncology understands why it's such a big deal. YOU'LL LEARN SOMETHING AWESOME TODAY. i am going to keep this as understandable (and simple) as i can. OPEN THE THREAD. 🧵
Cheers, chills, and a standing ovation when RASolute 302 showed unprecedented survival on daraxonrasib for patients with progressive pancreatic cancer Seldom do you sense you’re witnessing a historic moment in cancer care but this feels like ras targeting has arrived #ASCO26
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1/5 I'm a cardiologist. I have spent twenty years watching cholesterol destroy arteries, trigger heart attacks, and kill people I care about. Today, Eli Lilly presented data that may begin to end that era. VERVE-102. A single infusion. One dose. It uses base editing to permanently turn off the PCSK9 gene in your liver. Presented today at the European Atherosclerosis Society Congress: 88% reduction in PCSK9. 62% reduction in LDL cholesterol. Sustained up to 18 months. No treatment-related serious adverse events. One infusion. Not daily pills you forget to take. Not monthly injections. One dose — and your cholesterol may stay low for the rest of your life.
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Ryan Spangler retweeted
A few random notes from claude coding quite a bit last few weeks. Coding workflow. Given the latest lift in LLM coding capability, like many others I rapidly went from about 80% manual+autocomplete coding and 20% agents in November to 80% agent coding and 20% edits+touchups in December. i.e. I really am mostly programming in English now, a bit sheepishly telling the LLM what code to write... in words. It hurts the ego a bit but the power to operate over software in large "code actions" is just too net useful, especially once you adapt to it, configure it, learn to use it, and wrap your head around what it can and cannot do. This is easily the biggest change to my basic coding workflow in ~2 decades of programming and it happened over the course of a few weeks. I'd expect something similar to be happening to well into double digit percent of engineers out there, while the awareness of it in the general population feels well into low single digit percent. IDEs/agent swarms/fallability. Both the "no need for IDE anymore" hype and the "agent swarm" hype is imo too much for right now. The models definitely still make mistakes and if you have any code you actually care about I would watch them like a hawk, in a nice large IDE on the side. The mistakes have changed a lot - they are not simple syntax errors anymore, they are subtle conceptual errors that a slightly sloppy, hasty junior dev might do. The most common category is that the models make wrong assumptions on your behalf and just run along with them without checking. They also don't manage their confusion, they don't seek clarifications, they don't surface inconsistencies, they don't present tradeoffs, they don't push back when they should, and they are still a little too sycophantic. Things get better in plan mode, but there is some need for a lightweight inline plan mode. They also really like to overcomplicate code and APIs, they bloat abstractions, they don't clean up dead code after themselves, etc. They will implement an inefficient, bloated, brittle construction over 1000 lines of code and it's up to you to be like "umm couldn't you just do this instead?" and they will be like "of course!" and immediately cut it down to 100 lines. They still sometimes change/remove comments and code they don't like or don't sufficiently understand as side effects, even if it is orthogonal to the task at hand. All of this happens despite a few simple attempts to fix it via instructions in CLAUDE . md. Despite all these issues, it is still a net huge improvement and it's very difficult to imagine going back to manual coding. TLDR everyone has their developing flow, my current is a small few CC sessions on the left in ghostty windows/tabs and an IDE on the right for viewing the code + manual edits. Tenacity. It's so interesting to watch an agent relentlessly work at something. They never get tired, they never get demoralized, they just keep going and trying things where a person would have given up long ago to fight another day. It's a "feel the AGI" moment to watch it struggle with something for a long time just to come out victorious 30 minutes later. You realize that stamina is a core bottleneck to work and that with LLMs in hand it has been dramatically increased. Speedups. It's not clear how to measure the "speedup" of LLM assistance. Certainly I feel net way faster at what I was going to do, but the main effect is that I do a lot more than I was going to do because 1) I can code up all kinds of things that just wouldn't have been worth coding before and 2) I can approach code that I couldn't work on before because of knowledge/skill issue. So certainly it's speedup, but it's possibly a lot more an expansion. Leverage. LLMs are exceptionally good at looping until they meet specific goals and this is where most of the "feel the AGI" magic is to be found. Don't tell it what to do, give it success criteria and watch it go. Get it to write tests first and then pass them. Put it in the loop with a browser MCP. Write the naive algorithm that is very likely correct first, then ask it to optimize it while preserving correctness. Change your approach from imperative to declarative to get the agents looping longer and gain leverage. Fun. I didn't anticipate that with agents programming feels *more* fun because a lot of the fill in the blanks drudgery is removed and what remains is the creative part. I also feel less blocked/stuck (which is not fun) and I experience a lot more courage because there's almost always a way to work hand in hand with it to make some positive progress. I have seen the opposite sentiment from other people too; LLM coding will split up engineers based on those who primarily liked coding and those who primarily liked building. Atrophy. I've already noticed that I am slowly starting to atrophy my ability to write code manually. Generation (writing code) and discrimination (reading code) are different capabilities in the brain. Largely due to all the little mostly syntactic details involved in programming, you can review code just fine even if you struggle to write it. Slopacolypse. I am bracing for 2026 as the year of the slopacolypse across all of github, substack, arxiv, X/instagram, and generally all digital media. We're also going to see a lot more AI hype productivity theater (is that even possible?), on the side of actual, real improvements. Questions. A few of the questions on my mind: - What happens to the "10X engineer" - the ratio of productivity between the mean and the max engineer? It's quite possible that this grows *a lot*. - Armed with LLMs, do generalists increasingly outperform specialists? LLMs are a lot better at fill in the blanks (the micro) than grand strategy (the macro). - What does LLM coding feel like in the future? Is it like playing StarCraft? Playing Factorio? Playing music? - How much of society is bottlenecked by digital knowledge work? TLDR Where does this leave us? LLM agent capabilities (Claude & Codex especially) have crossed some kind of threshold of coherence around December 2025 and caused a phase shift in software engineering and closely related. The intelligence part suddenly feels quite a bit ahead of all the rest of it - integrations (tools, knowledge), the necessity for new organizational workflows, processes, diffusion more generally. 2026 is going to be a high energy year as the industry metabolizes the new capability.
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a private equity fund that buys businesses and just forces everyone to use claude code
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Ryan Spangler retweeted
BREAKING: Elon Musk considers buying Ryan Air and replacing the CEO with someone named Ryan.
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Ryan Spangler retweeted
Replying to @Ryanair
Should I buy Ryan Air and put someone whose actual name is Ryan in charge?
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SOUND ON. You’re hearing the first howl of a dire wolf in over 10,000 years. Meet Romulus and Remus—the world’s first de-extinct animals, born on October 1, 2024. The dire wolf has been extinct for over 10,000 years. These two wolves were brought back from extinction using genetic edits derived from a complete dire wolf genome, meticulously reconstructed by Colossal from ancient DNA found in fossils dating back 11,500 and 72,000 years. This moment marks not only a milestone for us as a company but also a leap forward for science, conservation, and humanity. From the beginning, our goal has been clear: ā€œTo revolutionize history and be the first company to use CRISPR technology successfully in the de-extinction of previously lost species.ā€ By achieving this, we continue to push forward our broader mission on—accepting humanity’s duty to restore Earth to a healthier state. But this isn’t just our moment—it’s one for science, our planet, and humankind. All of which we love and are passionate about. Now, close your eyes and listen to that howl once more. Think about what this means for all of us.
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Ryan Spangler retweeted
A powerful conversation with @gwei_sha, Head of DeSci at @SeiNetwork, moderated by @_Chelseycrypto They dive into decentralization, inclusion, and the future of open science in Web3. Inspiring to see women leading critical discussions and shaping the next chapter of crypto $SEI #DeSci #Web3
šŸ’”ā€œDeSci needs to stay decentralized—and inclusive.ā€ We sat down with Eleanor Davies @gwei_sha, Head of DeSci at @SeiNetwork, to talk vision, values, and real talk on building a more open Web3. Women in crypto, advice for newcomers, and what’s next for DeScišŸ‘‡ šŸŽ¤ MOD by @_Chelseycrypto #DeSci #Web3 #Crypto #WomenInWeb3 #AuraSci
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Probably nothing
The Sei Foundation is in the process of placing its boldest DeSci bet yet. @Sei_FND is officially exploring the acquisition of @23andMe to defend the genetic privacy of 15 million Americans and ensure their data is protected for generations to come. We believe user data sovereignty is a matter of national security. When an American biotech pioneer faces bankruptcy, personal genomic data of millions becomes vulnerable to parties that may not share the same values of transparency and open access. Our vision: • Deploy 23andMe on Sei, the most performant blockchain built for web-scale applications. • Return data ownership to users through encrypted, confidential transfers. • Allow users to choose how their data is monetized and share in the revenue. This isn't just about saving a company, it's about building a future where your most personal data remains yours to control. We'll be sharing updates in the near future, notifications šŸ”›
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We have the potential to radically extend human healthspan in the coming decades using epigenetic reprogramming. Check out @newlimit's 2025 Progress Update. Incredibly exciting.
We just hosted our 2025 Progress Update toward radically extending human healthspan! teapawt.net/i/broadcasts/1kvJpywwl…
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