#495 Inside the Search for a 300% Lifespan Breakthrough - Dr Ben Blue

Benjamin Blue (0:00)

The dream drug might actually be two drugs where one has no lifespan and extension, but it primes you to be in a state where the then lifespan extending molecule works twice as good as it would otherwise. So how do you take our 100 percent lifespan extending intervention, and then you turn that into a 200 percent lifespan extension? I would say that those are the only two true interventions that have been shown directly to link to human longevity so far. You have undisputed effects where you couldn't argue some aspect of the data.

Siim Land (0:34)

Dr. Ben, welcome to the show.

Benjamin Blue (0:36)

Hi. Thanks for having me on. It's a pleasure to be here.

Siim Land (0:40)

Yeah. I'm happy to have you on the show and we discuss a lot of topics related to life extension and longevity on the podcast, and you are actually working on trying to extend the lifespan in rongworms at the moment with your company to figure out what is the next, let's say, miracle molecule that will also help to extend lifespan in humans. I'm happy to discuss these topics with you. Maybe we can start with your company that you started with Dr. Mac Caberline, Ora Biomedical. So what is it and what are you researching? Yeah.

Benjamin Blue (1:22)

Well, it's a pleasure and exactly like you said. So my career has really been built on trying to understand how and why we age, with the goal of figuring out what we can do about it as the functional endpoint of that. And so I did my PhD with Mac Caberline at the University of Washington. While we were there, you had this observation that so much work and admittedly good work was being done investigating known pathways and molecules that have the potential to extend human lifespan or human health span. So you think rapamycin metformin, things that I think you've talked about to your audience already in the past. But what we weren't seeing enough of was unbiased discovery, looking at areas of a chemical space that no one else could look at. What we wanted to do was build a tool and a system that could let us move at scale through that chemical space and do it in a way that was really, really efficient. From that central goal, we took a step back and we thought, well, what's the fastest we can get at the answer? We built a tool that was a mix of cutting edge robotics and artificial intelligence.

That let us go and start the screening process for new therapies with lifespan as the first endpoint. Now, this is different than the way most drug development or most therapeutic discovery works. Because most of the time, you find a, you take, let's say, rapamycin example, rapamycin hits the mTOR pathway. So then you go and you find other things that look similar to rapamycin or that affects the mTOR signaling in a cell that because you can do a bunch of cells at scale. But what that misses is the opportunity to find new things, but also whether or not that molecule can effectively work in a complex multi-tissue animal system like you and me. But you and me are hard to study and we take really long time to age, hopefully. And so we built this roundworm platform because the animals only live about three weeks. And what that lets us do is go through huge amounts of molecules very, very quick, using the molecules' effect on aging as the first go-no-go point for further investigation and development. And so while we start with roundworms, we immediately take our best-in-class hits, once they hit a more threshold. We shake it out. On the low end, it's 25 percent, but upwards of 50, 60, rarely a couple of times even 70 percent extension of lifespan in those. And then we take them into human cells and do the mechanistic work that is pretty straightforward to go and understand how and why that molecule works. And so Ora Biomedical has been running at this problem for about, we spent out just about two and a half, two years ago from the University of Washington. We found a bunch of new exciting molecules. And right now we're developing those at a couple of pretty exciting indications that you and I can think of talking. That's my 30,000th review of the company.

Siim Land (4:48)

Yeah, so you're basically doing accelerated discovery. And it's very hard to figure out what will extend lifespan in humans because we live so long relative to mice or roundworms. And roundworms live even shorter than mice do. So you can learn a lot of things fast if you test a lot of different compounds. How many molecules have you tested already?