The Key To Longevity Might Be In These Boxes

These are the heroes of our story. They live in a laboratory and are known as C57BL/6 mice. They've been bred to be docile and are more or less all identical twins. Lab mice do all kinds of things for science. Their sacrifice leads to new discoveries and therapies for humans. Let's go ahead and give them some thanks. These particular mice belong to RetroBio. It's a biotech startup backed by $180 million from Sam Altman. Retro is in the aging business, and it wants to make humans live healthier for longer. And with the help of these mice, we're gonna find out how. I started visiting Retro about 3 years ago. Some things about the startup jumped out at me right away. It had a funky office. And it had a funky laboratory built out of shipping containers and watched over by an HVAC monster. None of this is normal. And that's because of this guy.

I'm Joe Betz Lacroix. I'm CEO of Retro Biosciences.

Joe is a longevity guru, but in a good way. He's also a polymath and an unconventional thinker and operator. And this is what he seeks to do.

We are working to add 10 years of healthy lifespan to humanity.

Much of the research takes place in Retro's shiny new lab. Look at it. It's glorious. But the animal work still happens in the older digs. Some of this was born of necessity since Retro began during the pandemic. Some of this is also to do science fast and relatively cheap.

Yeah, so we're really into pace. Uh, we want to make medicines as soon as possible. And so what we did is just build labs, and then eventually we invited the city in, and they were like, Whoa, this is really cool. We've never seen this before. Um, but you guys probably ought to get this permitted.

The longevity and aging field can feel amorphous and ambiguous, sort of hypey over the years. And when you launched, I just felt like you want to put these boundaries around it and define the objective.

Absolutely. There is and has been a ton of hype in the longevity world. People are promising to help humans live for 5,000 years or whatever. And then meanwhile, there's a conservative biopharma world that's very incremental and one disease at a time. Any kind of thinking about extending the healthy lifespan of humans, they just don't look at it from that perspective.

Yeah.

I think 10 years is exciting enough to be motivating and is also within reach. Part of an art of the startup is to pick something that's new enough to be ready for a startup but not too far beyond reach so that you can actually accomplish it within startup timeframes.

How many containers total?

Mmm, I think maybe about 40. One of the first things that we did was to acquire a bunch of lab equipment by acquiring a company that was going out of business, and they had 5 beautifully equipped labs. Like, a really great thing about running the company with Sam was I could just call him up on a Thursday night and say, "Holy crap, we have an opportunity to buy a company, but I need to do it tomorrow morning," and he can be like, Yeah, do it. And that's a board meeting. So that's where a ton of our equipment came from.

So most biotech companies, some scientist in a lab has found this interesting molecule. We're going to raise some money to see how far we can push this thing. Either it works or it doesn't. You guys came out taking like a few shots on goal. And I mean, that was very much on purpose, right?

You can found a company on different premises. And in our case, the founding principle is is extending the healthy portion of human life, and the mechanism is any means necessary.

Yeah.

And so we've explored probably pretty deeply 6 different directions to achieve that. We found 3 of them that we're excited enough about that we're taking them all the way to the clinic now. The first is an orally available drug that restores the cellular recycling of old and broken proteins. The other 2 are more strictly based on cellular cell replacement. So we can generate young cells outside the body and then replace older cells inside the body by putting them where they need to go.

Much, although not all, of Retro's technology revolves around work with something known as an iPSC. We don't love acronyms on this show, but this is one that you need to know because iPSCs are at the heart of a ton of current biotech bets from the likes of Retro, New Limit, and Altos Labs. To help explain these things, I've recruited Retro's computational biologist, Alex Trapp. He has some sweet computational mutton chops, and you'll hear more from him later. But for now, we give you IPSC 101.

I'm gonna try to explain it, and then Alex, who actually knows things, will fix everything. That I get wrong. There are these things called induced pluripotent stem cells. They're always shortened as iPSCs. You can take any cell on your body, a skin cell, heart cell, whatever, hit it with these 4 proteins, we call them transcription factors, and then what happens?

Uh, it rejuvenates the cell to its youngest possible state and also makes it into a stem cell. And from that stem cell you can generate any other type of cell that you'd like. I think this is going to be critical for any cell replacement therapies and really a big paradigm shift in biology.

So there you go, iPSCs. Remember that, you're going to hear it a lot.

Now that you have the basics, we're going to dive deeper into iPSC land.

Can I touch this wall?

Yeah.

And we're going to look at one of Retro's most promising programs. This is an effort to reproduce the cells that live in our bone marrow. And keep our bodies functioning at the most basic level. Our guide here will be Retro's Russian-born scientist, Anastasia.

So there is a lot of things that go wrong with age. One of the biggest and the recent developments is that there is mutations that accumulate in the bone marrow and other tissues as well. It's not good.

Okay.

So it links to worse survival outcomes, cardiovascular problems, and other diseases of aging. So with our approach, we can punch your skin, isolate cells from your skin, then we convert these somatic cells into pluripotent cells. And pluripotent cells, you can think of them as like embryonic cells. So when the embryo develops, it can develop any tissue you want.

And we just take those cells and replace them with those new, more functional It seems like so far this has been, been maybe the most promising line of discovery that you guys have been chasing after?

I would say I'm most excited about this one. It's working in mice, and working in mice doesn't mean it's gonna work in humans, but that's a hope. Yeah.

Yeah.

And we aim to go into patients 2 years from now.

So what kind of mouse is this?

The C57 BL6, colloquially known as the Black 6. They've been bred for, you know, hundreds of generations in the lab, so they're like pretty chill being in a cage. That's like normal life for them.

What is this thing? The rotorod?

This is a rotorod. So it's sort of like that lumberjack thing where you're standing on the log that's floating on the pond, and then it slowly turns faster and faster. And the young'uns are like, "Hey, I got this!" And you know, they're kind of like Having fun doing the, doing the, like, "I'm the best." At a certain point, the old ones are like, "Whoa, I'm out of here," and then they flop down, and then that's their score. And then maybe you do it for 20 youngs and 20 olds. You just see the difference in, you know, the clusters of the different amounts of time that they could stay on, and that's how well your therapy is doing.

Even to me, as somebody who's covered longevity for a long time in different shapes and forms. It felt like something changed 5 years ago where you had this new breed of longevity companies appearing.

I mean, this is the time to do science fiction in biology. For the first time, it's not science fiction anymore and it's real. And we're really at the frontier of being able to massively impact human health beyond just diseases, like impacting aging itself. Not everyone is born with the same set of circumstances, and to be able to give people more years of happy, healthy life with their families and with their professional work and all these things, just so meaningful.

Alex may be an optimist, but hopefully you can tell he's also quite rational and smart. He's not alone in being one of many people in Silicon Valley and elsewhere who think that now is very much the time to make this longevity technology a reality. This isn't all blood boys and Bryan Johnson's olive oil. It's the basics of living healthier, longer lives.