My current philosophy.

The biggest bottleneck in AI for biology is still the wet lab. AI can generate more ideas than our labs can test. Closing that gap is how we turn better models into faster discovery. Today, we’re introducing X-Automate at Xaira: bringing agentic AI and physical robotics into the lab. 🧵

Next step: Longevity and Rejuvenation. We are almost there. Researchers in Bonn turned blood cells from an 80-year-old into neural stem cells with a molecular age below 20. More than 60 years younger by epigenetic clocks, which estimate age from chemical marks on DNA. The team directly reprogrammed blood precursor cells into neural stem cells, skipping the usual pluripotent stem cell stage. The rejuvenation unfolded gradually and could be tracked for over 100 days.

A reported mountain lion sighting triggered an emergency lockdown at a Washington elementary school, though the formidable predator was ultimately revealed to be nothing more than an exceptionally large, domestic orange cat. The incident unfolded in November 2023 at Groff Elementary School, located in Moses Lake, Washington. School administrators placed the campus on a strict lockdown after an individual reported seeing what closely resembled a wild cougar prowling near the school grounds. For safety reasons, students and faculty were secured indoors while law enforcement and school officials thoroughly swept the surrounding property to evaluate the potential threat. The tense situation dissolved into relief when authorities finally located the suspected apex predator. Rather than a dangerous wild animal, the creature turned out to be an oversized orange house cat, which was casually spotted eating a rat near the campus boundary. Fortunately, the entire event concluded without injury, and regular school operations resumed promptly once officials confirmed that no mountain lion was present in the area. Subsequent community updates shed more light on the situation, with neighborhood residents identifying the chunky orange feline as a local outdoor pet named George.

I am flattered and optimistic about inclusion in Forbes’ list of American Optimists. (35). The American ideal is driven by the belief that the future will be better than the past, and individuals, not the State, are the drivers of that change. It is self-fulfilling. Only the State can blunt the optimism and slow the progress.

Optimism is at the heart of the American dream. In that spirit Forbes is recognizing the country’s 250 Greatest Living Optimists. These are founders who took a big risk on new possibilities, investors who prioritize long-term value over short-term gain, market-minded philanthropists and educational pioneers. #Forbes250 Read more: forbes.com/sites/alexknapp/2… Illustration: Lina Jaradat for Forbes; Photos: Guerin Blask for Forbes, Cody Pickens for Forbes, Jamel Toppin for Forbes, Martin Schoeller for Forbes, Tim Pannell for Forbes

Meet X-Scientist: our step toward a self-improving virtual drug hunter! Today, we’re introducing Xaira’s agentic AI platform for drug discovery: 🧠 Beats Codex using the same Astra model by 7.4 percentage points on DrugDiscoveryBench. 🧬 Nominates targets ~10× faster than human curation, with a comparable wet-lab hit rate. 🔁 Conducts autonomous research, outperforming AutoResearch and AutoScientists in the PerturbQA benchmark. Here’s what we built, what we tested, and where we’re going. 🧵

Congrats to $RAPP @ceesay_abe, @T_Ignelzi, & Steve Paul on data this morning in bipolar mania. The trial met the primary and secondary endpoints with statistically significant placebo-adjusted improvements at Week 3 in the YMRS total score (3.1 points; p=0.045) and CGI-BP Severity of Mania score (0.4 points; p=0.024). This is following great data in focal epilepsy.

A guy built an AI that thinks it’s 1899, then tried to get it to beat Einstein to his most famous theories.

In 1983, a BBC interviewer asked Richard Feynman why two magnets push each other apart — and he refused to answer it. What he did instead is the best seven minutes on thinking ever filmed. Bookmark & watch today, no matter what.

Next year, I will give one of my SpaceX shares to every kid in America. This will be the first of many.

Only about a quarter of human diseases have an approved therapy. By some estimates it's a few percent. Most of those treatments slow a disease rather than stop it. Closing that gap is what the AI-cures-everything story promises. Build a system smart enough and the cures hidden in what we already know will fall out. I have worked at the intersection of machine learning and biology for three decades, and I believe #AI will eventually transform human health. The capabilities arriving now are extraordinary. But the promise rests on an assumption that is simply false: that we already understand human biology well enough for a clever enough reasoner to find the answers in it. We don't. More than 90% of drugs entering clinical trials fail, a number that has barely moved in decades. In the large majority of those failures the molecule was engineered just fine. The mechanism it targeted was wrong. We are doing a pretty good job at manufacturing keys, but they are generally for the wrong locks. And because nobody wants to fail in the clinic, the industry has retreated to the locks it already trusts: 38 targets now have more than 50 programs against each of them, while the number of novel targets advanced per year fell from roughly 100 in 2015 to about 30 in 2024. AI will not reason its way past this. Biology wasn't engineered. It is the product of billions of years of messy, stochastic evolution, and the variation that produced is too vast and too idiosyncratic to work out in the abstract. You have to measure it. Aimed at a biology this thinly sampled, AI will mostly help us generate failures faster. I founded @insitro because getting to the right locks requires a different kind of system. We generate multimodal human and cellular data at scale, use machine learning to find causal drivers of disease, and test those hypotheses experimentally. Virtual Human™ is built for causal discovery; TherML™ turns what it finds into the right therapeutic intervention. It is working: first-in-class programs internally and with partners, three #ALS targets that Virtual Human™ identified and @bmsnews nominated, and additional collaborations with @EliLillyandCo and @GileadSciences . Today we are launching Deep Phenotype: Scaled Biology, Deep Causality. Issue one is "Drug Discovery Has No Magic Wands," the first half of a two-part essay on the magical thinking currently running through our field and what I think it will actually take. After that you will hear from insitro's own scientists and engineers, people who work across computation and experiment because the problem requires both. Getting this right is hard, and we do not have all of it worked out. I hope you will follow along and think it through with us. DeepPhenotype.Substack.com

AstraZeneca Strikes Up to $1.5 Billion AI Drug Discovery Deal With Insitro on.wsj.com/4B96TET

Inside a human brain when reading a book.

If you travel the world, our drama pales to most everywhere. We are self correcting, messy, flawed, innovative, free. Much of Europe has lost its way and is losing control. We should not emulate it.

FRANCE: Rioters have set fire to the historic City Hall in Limoges, France, causing its roof to burn and its clock tower to collapse. Built in 1883, the 143 year old landmark survived 2 world wars and was designated a protected historical monument in 1975. It’s gone now.

There is a throwaway line in a WSJ story about the Seattle mayor’s failures about how reps from her admin traveled to SF to learn how Lurie was leading such a successful turnaround and were stunned by how it seemed to be connected to hiring competent people who know what they’re doing.

The more you see it, the wilder it is..😲 Incredible.

In-vivo CAR-T is the rage and it may work, but it is not clear it has the durability or long-term efficacy of ex-vivo. In general, I bet ex vivo in multiple applications will get cheaper and will win in some big verticals.

Congrats to City Therapeutics (CTY), co founded by John Maraganore, ARCH Venture Partners, AN Ventures, Mayu Yoshikawa, Ari Nowacek and others. Great example of Japanese and American collaboration.

JUST IN: Elon Musk unveils the Tesla Roadster by launching it off a ramp before the car flipped in midair and safely landed on the ground. The car is a collaboration between Tesla and SpaceX. One of the most insane things I've ever seen.