Hi friends 👋 , Happy Friday and welcome back to our 196th Weekly Dose of Optimism! A new American nuclear reactor has gone critical. Dan and I are doing a Hyrox in a few hours. New York City is hot and buzzing. What a week for the optimists.Let’s get to it. When it comes to implementing AI within your company, most orgs struggle with a knowledge problem. You can plug in all the AI tools you want, but if your internal info is scattered, outdated, or contradictory, you just get the wrong answers faster.Guru fixes that.It’s a central, governed knowledge layer that sits underneath your tools and actually makes them useful. Teams like Spotify and Brex use Guru to:Keep company knowledge in one place (and actually maintained)Verify information so it stays accurate over timePower AI tools with trusted, up-to-date contextDeliver answers with sources, not guessesFix the input once with Guru, and it improves every output, across every tool your team uses. If you’re investing in AI, Guru can help make it actually work.Try Guru TodayBig day for the U S of A, and for our friends at Antares. Last night, Antares announced that its Mark-0 low power reactor was brought to criticality at Idaho National Lab with a self-sustaining fission reaction. In doing so, it became the first novel reactor design to undergo a fueled test in over 50 years. “We are now the first reactor to meet the intent of President Trump’s May 2025 EO 14301,” CEO Jordan Bramble said, “which calls for three reactors to meet this milestone before America’s 250th birthday on July 4, 2026.” This is a massive milestone, and one that seemed implausible even a year ago. It’s also just the beginning - more reactors will go critical in the coming month, and Antares itself is moving from testing to producing electricity. Or as Jordan put it, “We’ve made neutrons. Next up: electrons.” Two and a half years ago, Julia DeWahl and I started a podcast called Age of Miracles to try to understand why America no longer made this miracle technology, and what it might take to change that. We talked to most of the founders in the space, some of whom are racing to criticality alongside Antares. Turns out, Julia, the co-founder of Antares, was the one who pulled it off, alongside Jordan and the rest of the team. It is an incredible accomplishment to go from “Why aren’t we doing this?” to doing it - going critical - in under three years. I’m very proud of Julia for making it happen, and excited for the country now that we’re producing new nuclear in America again. 🇺🇸Ashlee Vance for Core Memory There are no approved treatments for alcohol-related liver disease. It kills 30,000 Americans a year, about 40% of the population has some degree of fatty liver, and nothing. Until now. NewLimit, the epigenetic reprogramming company co-founded by Coinbase CEO Brian Armstrong and computational biologist Jacob Kimmel, just closed a $435 million Series C led by Founders Fund with Thrive, Greenoaks, and others at a $3.1 billion valuation, more than triple what the company was worth a year ago. For good reason - NewLimit is going into human trials with the first-ever test of an age-reprogramming medicine in human subjects, starting in 2027 in Australia, after success in mice. NewLimit fed old mice alcohol as their sole calorie source for 11 days and then gave them a binge dose. The untreated old mice flipped onto their backs and stayed sedated for 8 to 12 hours, like me if I have a couple drinks now. Young mice on the same protocol just popped up like it was nothing. But when old mice got a single dose of NewLimit’s therapy, RNA encoding specific transcription factors, delivered via lipid nanoparticles, they stopped passing out. They were as good as young. As Kimmel told Ashlee Vance on Core Memory, “It is just binary. They’re either passed out or they’re not.” The therapy didn’t help them metabolize alcohol faster. It restored the liver cells’ intrinsic ability to withstand stress and regenerate, as if they were young again. The discovery engine behind those transcription factor combos is an AI model called Ambrosia that ingests published gene-function literature, protein sequences, and DNA binding motifs, then trains on roughly 10,000 real lab experiments. It explains more than half the variation in results and can be run in reverse: you specify the cell state you want, and Ambrosia proposes the combination most likely to produce it. As frontier LLMs and protein-folding models improve, the embeddings Ambrosia feeds on get better for free. NewLimit initially expected a decade-plus timeline to reach the clinic. They’re now five years ahead of schedule. The first indication will be steatotic liver disease delivered via a 20-minute IV infusion, with the long-term goal of a subcutaneous pen for broader GLP-1-like use. Beyond the liver, they’re engineering nanoparticles to target blood vessel lining (with a focus on chronic kidney disease), T-cells (autoimmune conditions), and eventually the blood-brain barrier. The sooner they get through their roadmap, the longer we all live. Amrith Ramkumar for WSJAI for bio will be used for a lot of good. We need to prevent it from being used for bad.The leaders of the big AI labs don’t agree on much these days. Over the past week, for example, OpenAI CEO Sam Altman said that he doesn’t like Anthropic’s telling everyone they’re going to lose their jobs in one interview and that AI budgeting has become a huge issue for some companies, which would hurt both OpenAI and Anthropic but which I think he’s probably OK saying out loud because Anthropic is the one that just filed an S-1. “Sam Altman. You could parachute him into an island full of cannibals and come back in 5 years and he’d be the king.”One thing they do agree on, though, is that people shouldn’t be able to use their products to make bioweapons. Sam, Anthropic CEO Dario Amodei, and Google DeepMind CEO Demis Hassabis are among the signatories on a new letter urging Congress to pass laws that would require companies that sell synthetic DNA and RNA to screen their customers and block any combinations that could be dangerous.Per the WSJ, “Trump previously revoked a Biden-era executive order that resulted in a gene synthesis screening framework. The White House last year said it would replace the Biden framework with its own screening guidelines but hasn’t yet published a replacement policy.” Congress should probably go ahead and just do this. “AI is going to kill us all” is better left an Anthropic marketing tactic than a real scenario. On Age of Miracles, one of the people Julia and I interviewed was Helion CEO David Kirtley. Coming in, we’d heard from people in fusion that Helion was brash, and more “Silicon Valley” than others. Its SpaceX-like cadence of building new generations while still testing older ones was aggressive.We both came out of the interview incredibly impressed, and believing he might just pull it off.This week, Helion got one step closer. It announced a $465 million Series G led by Thrive Capital (big week), bringing its total funding to $1.5 billion and valuing the company at $15.5 billion. In February, its Polaris became the first privately developed fusion machine to demonstrate measurable deuterium-tritium fusion and hit plasma temperatures of 150 million degrees Celsius, or ten times the heat of the core of the sun. It’s also the first private fusion machine to operate with D-T fuel, after becoming the first company to receive regulatory approval to possess and use tritium for fusion energy production. Meanwhile, Orion, Helion’s 50-megawatt facility in Malaga, Washington and first commercial fusion power plant, is already under construction, with a contract to sell electricity to Microsoft starting in 2028.Helion will use the money to scale manufacturing from Polaris, which proved the physics, to Orion, which is an actual power plant that aims to produce electricity that customers actually use using the same energy-generation process used by the sun. It’s fusion, and it’s really hard, and there’s lots to prove, but the funding will help the company take a swing at the goal Kirtley laid our in our conversation: to make “generators per day rather than generators every few years” by 2030. Ab sole. Frontiers in NeuroscienceAn octogenarian Japanese-American woman with a 10-year history of Alzheimer's disease, including five years of near-total functional decline, monosyllabic speech, chronic urinary incontinence, flat affect, and dependence in virtually all daily activities, was given a single 5-gram dose of psilocybin mushrooms. Nineteen hours later, after fits of intense sweating, she woke up and “the patient spontaneously initiated autobiographical conversation lasting several hours.” Over the following days and weeks, her urinary continence came back after five-plus years, and she began walking independently, dressing herself, sustaining eye contact, retrieving contextual memory contextual, and engaging emotionally. A second session a month later produced spontaneous humor, vivid emotional imagery, and increased agility. She told her caregivers, unprompted: “It is pleasant to come here.”This was a single case and not a clinical trial. The authors are careful to note that causality can’t be established, and the improvements were transient. Whether or not it was the mushrooms, what’s incredible is that, even after 5 years, her capacity for all of those things was still in there. As the researchers put it, “Residual functional capacity may persist in advanced Alzheimer's disease and may become transiently accessible under specific neuromodulatory conditions.” My grandmother had Alzheimer’s, and me and my loved ones getting it is one of my biggest fears, so any good news about this terrible disease is welcome, and I want to believe. If taking some mushrooms helps fight Alzheimer’s, sign me up for the clinical trials. EXTRA DOSES: No Science Breakthroughs this week (back next), but we have a lecture on the grid & batteries, MAFIA, Hoffman, and Resonant Computing below…