The Backlash David Sinclair Faced from the Scientific Community | Joe Rogan

How many people do you think worldwide are working in your field? So in terms of leading labs, there's about 20, 30. Broadly, there's probably a few hundred labs. And are they all in essentially the same field of study? They're all working with the same molecules and the same parameters? Not everyone works with molecules, but what I can tell you is we get together in conferences and we talk about discovering a new gene that extends lifespan and a new molecule that's working in mice or sometimes in humans. But it's a big field now. It's grown. And when I started, it was the backwater of biology, antioxidants, etc. I was very lucky to start when it was really small and stick it out. There was a fair amount of criticism in those days. How so? Like that it was... Well, like a lot of my friends, my supervisor said I was insane for working on aging. That's not a thing. That's not biology. Really? Yeah. Wow. How long ago was this? So I came to the U.S. from Sydney in 1995. Went to MIT. And the scientists in the lab that I joined, Lenny Guarentee's lab, two students had just started working to figure out why yeast get old. And I joined as the third senior person to join. And all the other people in the lab, there are about 18, 19 people, they said, you are nuts. Lenny's lost his mind. He's working on aging. That's not a thing. You should be working on what we do, which is understanding how genes are regulated. So I called up my mom and I said, I think I've made a big mistake here. I thought this was the thing and the guy and everyone here says he's nuts. Meanwhile, you were right. Well, you've got to take some risks in life. That's one lesson. Yeah, but that's an interesting one, right? Because you were a young fellow. He didn't really totally know. It was pretty lucky because I'm in Australia, right? I don't know what people are saying about this lab until I get there. But I've always been fascinated with aging since I was four. Well, now though, with all the promising new discoveries, I mean, they have to be eating crow, as it were. You ever talk to those people? They go, hey, fuckface, I was right. You don't call them up in the middle of the night drunk. No, I definitely forgive people too much. I've had some pretty big enemies along the way, but I try to be nice. Is it because research and this sort of scientific work is so competitive? Yeah, it is. It is. And there's this belief that someone's success is your failure. It's not really that is the case. That exists in show business too. It's a weird sort of mindset. It's a very limiting mindset. Right. And also, and this may be true in Hollywood, in science, if you come up with a new idea when you're young, you're a young Turk, and you're upsetting the status quo. The Thomas Kuhn's book on the structure of scientific revolutions just had it right. He wrote it in the 60s about chemistry and physics, but it applies to biology. If you come up with a new theory that's that disruptive, the current leaders will attack you, and it's a period of chaos, and you just have to get through it. And fortunately, I'd read Kuhn's book, and I knew that this was normal. But a lot of people around me were saying, oh no, people are saying we're wrong, and it's controversial. We don't want to be controversial. I'm like, controversy is great. Let's do more of that. And if it's not controversial, I want to do it. That is interesting. Do you think that's because the people who are the old guard are upset they didn't find it themselves, or they're upset that your new findings will make their work look irrelevant? Yes, it's probably a bit of both, but mostly it's that they're worried that their lives will have been in vain if what you're working on is not true. Right. Yeah, there's an amazing documentary on the Sphinx, where these geologists are talking about some of the water erosion outside the area of the Sphinx, and they're saying this points to the fact that construction was thousands of years older than they thought. And you see this one Egyptologist freaking out. He's freaking out, like, what evidence? What evidence of this culture are you talking about? Because apparently it would have predated the known dates of 2500 B.C. would have made it like 7000 years older than that, because it would have to be back when there was rainfall in the Nile Valley. And you could see this guy's ego kicking in because he was a professor, he had been teaching Egyptology, and he was freaking out. Instead of examining this evidence, like, wow, like talking to this geologist who studies rocks and erosion, who's really steadfast, he's a Boston University geologist, Dr. Robert Chalk, and he's saying this is evidence of water erosion, and he's showing it, and he even showed it to a bunch of other geologists, and they all agreed. And this guy, this Egyptologist, in this documentary was freaking out, and I was like, wow, that's what happens when you think your whole life's work is horseshit. Yeah, it can be a blow to the ego. I haven't lived through that yet. It's probably coming. But what I've noticed is that the really successful scientists and people in life just embrace change and go with it. Yeah, you kind of have to. I mean, it doesn't mean that that guy is a loser. It just means he was acting on incorrect information based on what they knew before. I mean, he should embrace it and say, look, well, we know certain things were built at 2500 B.C., like the Great Pyramid, that's been pretty clearly established, but it looks like there were some ancient structures that were there even before then. Now we have new things to study. They don't look at it that way, though. Yeah, see, the problem with how biology and actually most facts are taught or theories are taught is that there's a textbook and that's the Bible equivalent. What I try to teach my students is, can you please just forget everything you've just learned? And what's important to know is that most things we think we know are not correct. They're going to change over time. All theories change. Newton was wrong, but he helped us get here. Expect that we only know 0.01% of what we need to figure out and a lot of what we think we know is wrong anyway. So even if you have the greatest theory, expect that it will be overturned, but you can at least cherish the fact that you've helped us get to that point because without Newton we wouldn't have quantum physics. Well, for someone like me hearing you say that, it's very promising and it's very encouraging. But I always thought that scientists were always going on just data. All they cared about was data. All they cared about is what is correct. And that was what was crucial. That's what's important. This is what they talk about. This is what they study. When I found out that scientists would ignore information or use their own personal biases against information or attack research because it somehow negates what they've done, it's very disheartening. For someone who's not a scientist, you go, oh no, the ego is in science too. Right. It's disheartening as a scientist, I can tell you. There was a time of great change in the aging field where we discovered genes control aging and molecules like resveratrol could extend health and lifespan. It was brutal. I'd get up and I'd give a speech and someone would say, you're wrong. Where are they now? Do you call them up in the middle of the night? Call them up. You dumb motherfucker. Have a couple of glasses of wine. I think the secret to success in life is actually just existing for long enough and all your enemies just fall away. Yeah. Well, they die. They're not into anti-aging. They all look like shit and they can't walk anymore. They just have to outlive your enemies. It's an easy way. That must have been a tough time though for you as a young man. You're hearing this from these established scientists and part of you must have been thinking, geez, are they right? Sure. You have to entertain the possibility that you're wrong, that that's what we do. But you go back to the lab and you retest it. I went through a really brutal period in my career where we had data, we interpreted it, we published it in the top journals and it was about how resveratrol works on that sort of 2N enzyme that I mentioned. And Pfizer came out with a paper that said, it's all wrong. And I had people call me up saying, it was nice knowing you, I'm really sad for you. It's over. Yeah, bad luck. And so I went back to the lab. We had some data already from years before which I knew were interesting. And it took another, I think, four years to get to the bottom of it. But it turns out in the end I was right. But there were days when I said, screw humanity, I can't even be bothered getting out of bed if this is how I'm going to be treated for trying to devote my life to the betterment of people's lives. It's tough. I think anybody who's in a position in their career like that has to have gone through really hard times. It's just discouraging from a non-scientist who relies on people like you, for someone like me who relies on the folks like you out there doing the hard work, who would face that sort of, I guess the best way to describe it would be ignorance. Well, it's okay for scientists to challenge a theory. That's what I did and what everybody is trained to do. But to do it in such a public and controversial – Vicious. It was vicious. It was definitely vicious. Even the words they used were vicious, which is really hurtful. But they're wrong. Well, they might have been right. But they were wrong. Call them up. Mill and I, you dumb motherfucker. Yeah. The person who published that paper, I do think about meeting that person again. What are they doing now? But it can destroy careers. It's not just – it's tough. You can run out of money. Your students go away. Sure. That was happening to my life. We went down to four people. And what was the high? I mean, these days I'm – But what were you then? Before then it was about 1820. And you went down to four? Four. So it was looking bad. Oh, yeah. People had written me off. Holy shit. But you were right. Well, you've got to push forward. You've got to get lean because you're not going to get government funding for a while because people think that you're a failure. God damn. That's crazy. Well, science is not for the faint of heart. I would imagine. Yeah. Yeah. Boy. Thick skin. Thick skin. Stubbornness. Only those survive. What was the turnaround? Was there a moment where it turned around and moved into your – Was it your favor? Yeah, there was. There was one day when it all changed. So the earlier data – so we're data driven. The early data was that the enzyme – we could mutate or change the enzyme so that it wasn't going to be activated by resveratrol. And we found that mutation. Now that just technically – or non-technically means that we could change the enzyme in a way that wouldn't work. So we then put that non-working enzyme into a cell. And now we have a mouse that doesn't work. And we give it resveratrol. And if it works, it means I'm wrong. If it doesn't work and it's blocked by that change in the enzyme, we're probably right. And that's what we did. But the real change was that there was a company that I started that was making drugs, the one that cured – or at least seemed to cure psoriasis. And they had made these very synthetic molecules that were not related to the plant molecule or resveratrol. And so I said to myself and to the student who was working on it – a very brave student – if the change in that enzyme also blocks the drug, then we're on to something. Because that means two separate groups working on separate types of molecules, different people, different systems, all get blocked by this one little change in the enzyme, then we're right. And so he walked over to the company, got the molecule, threw it on the enzyme, and it didn't work on the mutant. And that was me rejoicing because I could say there was a universal activation mechanism on this one enzyme. Resveratrol works. The molecules at the company work. And now there's an interesting thing that just came out from Spain that metformin, the diabetes drug, may actually work the same way as these other molecules by activating our favorite enzyme, the sirtuin. Wow. And how much time were you in the dark lands? It was a couple of years of hell. Yeah. Right. It gets so bad because you've got this tight-knit group of scientists and you have lab meetings and you present your results and usually you're very supportive trying to help. I had one guy saying to my student, David doesn't know what he's talking about. You shouldn't work on this. It's been proven wrong. He was dead against me in my own lab. I'm paying his salary. And it's okay to be constructive but vicious within my own group. Well, suffice to say, he wasn't in my group for that long. Wow. Now this other guy that used all these other vicious words about you, where's he at now? Not sure. I would know. I would know. No, I don't have time to look back. I'm looking forward. You're nicer than me. Yeah. You know what? In science, because it's very collaborative and often your enemies are reviewing your own work. If you build up too many enemies, you won't survive. No, it's definitely a healthier approach. I'm kidding. I probably would do exactly what you did. But it still has got to be beautiful to come out on the other end and be proven correct and actually be at the forefront of these emerging technologies. Well, it is. I don't rest on any laurels but what I do is I pause and I remember how hard it was to get here and how fortunate I am to have made it this far. And I'm working with hundreds of collaborators around the world to make this come true, this idea that we can really treat aging and prevent deterioration. So I'm blessed. I have an app on my phone that I've helped engineer. What's that? It's called Lua, L-U-A. What is that? It's a little company that we bought in New York and nurses and dentists use it to pass medical information around. But we use it to share information between scientists around the world and coordinate activities between companies that I started. Yeah. So I think I mentioned to you that I've started a few companies. What I'm trying to build are companies that are the 21st century version of a pharma company that is actually has a decent reputation in the world. I think it's pharmaceutical companies, whether it's deserved or not, have a pretty bad rap. I'm trying not to fall into that trap, but I'm also trying to use 21st century technology to not become too bureaucratic as well within the organization. That's what the Lua app offers us.