Hi friends 👋 ,
Happy Friday, welcome to the 197th Weekly Dose of Optimism, and a very Happy SpaceX IPO Day to those who celebrate!
It’s been a big week over here at Not Boring HQ. On Monday, we published a co-written essay on flying cars with Tsung Xu. On Wednesday, we published one on tokenminning with Markie Wagner. That night, I got to go to the craziest basketball game I’ve ever seen. Yesterday, the World Cup started right here in America.
And today, we have wall-to-wall, handcrafted optimism for you, brought to you by our new friends at Pangram, who are allies in the fight against AI-written slop.
We have a church that has taken lifetimes to build, and a trial of a drug that may help extend our lifetimes. We have Doudna back at it with a cancer-shredding CRISPR. We have drone boats saving soldiers, and autonomous planes that fly right over the water. We have money for robots and Bezos has money for manufacturing. And we have Science Breakthroughs, a view of America through Freddy’s eyes, nuclear batteries, and even more. What a week for the optimists.
Let’s get to it.
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(1) Pope Blesses La Sagrada Família’s Tower of Jesus Christ
This week, to mark the 100th anniversary of the architect Antoni Gaudí's death, Pope Leo XIV blessed the Tower of Jesus Christ at Barcelona’s Sagrada Família basilica. It LSF’s tallest tower, making it the tallest Catholic church in the world, and its central one. There’s more construction to be done on the rest of the church, but the ceremony was beautiful enough to lead off with, given how much I love the story of La Sagrada Família.
I wrote about it in I, Exponential back in August 2023. You can read the LSF section here.
In 1883, a small group of Catholic devotees of Saint Joseph (Josephites) entrusted a young Catalan architect, Antoni Gaudí, to build them a church. As architect Mark Foster Gage writes in a piece for CNN:
Gaudí’s vision of the church was so complex and detailed from the start that at no point could it be physically drawn by hand using the typical scale drawings so common to almost all architectural projects. Instead, it was almost entirely constructed through the making of large plaster models to communicate Gaudí’s desires to the army of stonemasons slowly liberating its form from blocks of local Montjuïc sandstone.
Then Gaudí was hit by a tram car and died in 1926, with the church only 10-15% completed. For the past century, teams of builders and architects and technologists have worked to figure out exactly what he was going for, and then to build it.
The reason I love the story, other than LSF’s beauty and the fact that Barcelona is one of my favorite cities in the world, is that the reason we’ve been able to get it to this point over the past half-century is that the technology finally caught up to what was in the architect’s head.
In 1979, a 22-year-old Kiwi Cambridge grad student, Mark Burry, visited Sagrada Família and interviewed some of Gaudí’s former apprentices. They showed him the boxes of broken model fragments, and offered him an internship. Burry got to work trying to reconstruct the mind of Antoni Gaudí in order to construct the church that lived within.
He tried to hand-draw the “complex intersection of weird shapes, including things like conoids and hyperbolic paraboloids” but he realized that the tool wasn’t up to the task. The computer saved the day.
Burry brought in software used to design airplanes to solve the otherwise-impossible problem of translating Gaudí’s sketches of bone columns into 3D models.
In order to actually construct the building, Burry and team hooked their computers up to a relatively new invention, CNC (computer numerically controlled) machines. CNC machines were themselves a product of a number of technological advances in computing power, data storage, electronics, motors, material science, user interfaces, networking and connectivity, control systems, and software designs. All of those curves converged in time for Burry to feed his 3D models into CNC machines that could precisely carve their designs out of stone.
Today, the team working on Sagrada Família uses a full arsenal of modern technology, from 3D printers to Lidar laser scans, from sensors to VR headsets.
And now, this great tech-enabled architectural wonder of the world has its central tower completed, is nearing full completion, and has the blessing of the Pope.
As impressive as the building itself is, the Pope blessed both it and his Nova Knicks in the same week. He’s the real MVP.
(2) World-first: therapy to make cells young again trialled in a person
Heidi Ledford for Nature
Five years ago, David Sinclair's lab at Harvard made old, blind mice see again by turning back the biological clock in their cells. They coaxed aged optic-nerve neurons to behave young again, and regrow.
This week, for the first time, they did it to a person.
Life Biosciences, the Boston company built on Sinclair's work, announced it has treated the first participant in the world’s first clinical trial of partial cellular reprogramming. The trial is targeting glaucoma, a disease that slowly kills the neurons of the optic nerve, which don’t typically regenerate. They’re betting that the therapy will make the cells young enough to try.
The work is based on Japanese Nobel Laureate Shinya Yamanaka’s eponymous Yakanama Factors, four genes that can rewind any adult cell all the way back to a stem-cell state. The problem is, a reset retina cell forgets it's a retina cell. So Life Bio uses three of the four factors (dropping c-Myc, the one most tied to cancer) and nudges the cells only partway back: younger, but still themselves. In Sinclair's 2020 mouse study, that partial nudge regenerated neurons and reversed vision loss in elderly and glaucomatous mice.
The approach - partial epigentic reprogramming - is similar to the NewLimit approach to curing mouse (and eventually human) hangovers and liver damage that we covered in last week’s Dose.
We flagged the potential for this trial when the FDA cleared it back in January. Now, there's a human being walking around with partially reprogrammed cells in their eye.
Before we get too excited, this is a safety trial, and it’s only in one patient so far. There are real concerns. Push cells too far back, or in the wrong tissue, and you risk tipping them cancerous. Longevity scientist Matt Kaeberlein put it plainly: the upside is big if it can be done safely, but the tech is early and the downside risk is severe.
That’s the only place to start, though, and the potential here is enormous. Two weeks in a row, we’ve covered credible teams pursuing trials to reverse aging, that horrible disease that ultimately kills every human on earth and degrades our quality of life in the process. The sooner we get these therapies, the longer we live younger.
(3) Doudna's Lab Build a CRISPR to Selectively Shred Cancer Cells
Andy Murdock for Innovative Genomics
Speaking of cells… this week Jennifer Doudna's Innovative Genomics Institute published a paper in Nature describing a CRISPR system that does the opposite of what it usually does. Instead of fixing a broken gene, it finds the cells carrying one and destroys them.
Most cancer drugs are inhibitors that tamp down an overactive gene. But the most common cancer driver is the reverse: a tumor-suppressor switch that's been snapped off. p53, the gene that normally keeps cells from turning cancerous, is mutated in roughly half of all cancers and up to 70–90% of the nastiest ones: ovarian, pancreatic, non-small-cell lung. You can't restore a lost function by inhibiting something, which is why, after 35 years of trying, there's still no p53 drug.
So first author Jingkun Zeng went the other way. He engineered CRISPR-Cas12a2 to watch for the RNA signature only a p53-mutant cell produces, and when it sees that signature, the enzyme shreds all the genetic material inside that one cell, killing it while leaving healthy cells alone. In a dish of cells differing by a single DNA letter, it wiped out the mutants and left the normal ones almost untouched. Because it's programmable, a new mutation just means writing a new guide RNA.
The caveat is that this is still cell culture, and as Zeng flags herself, the hard part will be delivery, first in animals, then humans, to get a big genome-cutting enzyme into every target cell in a living body.
But still! People have been trying to target p53 for 35 years. Doudna & Co have figured out a way to just shred it. Say it with me… get fucked, cancer.
(4) Saronic Drone Boat Rescues Downed Apache Crew
Nicholas Kulish and Eric Schmitt for The New York Times
On Monday, Iran downed an American Apache helicopter near the Strait of Hormuz, sending two crew members into the water. That’s bad news, not the stuff of the Dose.
The Dose-worthy part is that those two crew members were rescued by a drone boat, a Saronic Corsair. “It was the first U.S. rescue carried out by an autonomous surface vessel, remotely piloted by a human operator, the Central Command spokesman, Capt. Tim Hawkins, said on Tuesday.”
Per The New York Times, “The vessel carried the Apache’s pilot and gunner to another location, where they were picked up by a helicopter to complete the rescue.”
Again, two American military members were stranded in the water in hostile territory, and they were rescued by drone boats built by an American startup that we’ve covered previously in the Dose, just one week after the same company launched its much larger Marauder, which it built in an American shipyard (America is supposed to be bad at shipbuilding) in under a year.
If that’s what American Dynamism looks like, then all aboard. (jk they’re autonomous)
(5) Standard Bots Raises $200 Million at $1 Billion
Here at the Weekly Dose, we love when good things happen to our friends. A controversial stance, perhaps, but we stand by it.
So we were very happy to see our friend Evan Beard raise $200 million at $1 billion for Standard Bots, America’s largest manufacture of AI-native industrial robots. Evan said that the company is on track to deploy 10% of America’s industrial robots by 2027. That’s not saying as much as it should: last year, China installed 9x more robots than the US.
With the money, Standard Bots plans to manufacture robots - from metal in to robots out - and deploy them in manufacturers across the country. More robots, Evan argues, more competitive American manufacturing.
If you want to learn more about what Standard Bots is building and why their Many Small Steps approach might be the way to actually make robotics happen, check out the essay Evan and I co-wrote in January: