Laura Deming is a partner at The Longevity Fund. They invest in companies that will allow us to live longer and healthier lives.

You can learn more about them at Longevity.vc.

Laura’s on Twitter @LauraDeming.

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Topics

00:00 – Why focus on longevity now?

1:50 – How did Laura get started in longevity?

3:00 – Why raise a fund?

5:30 – What does Laura do personally for longevity?

8:45 – Worm and mouse studies

10:20 – Craig’s personal habits

12:15 – Human studies

15:00 – Mica asks – Do you think immortality is going to be achieved by: 1. Curing all disease and stop aging so we could live with our own bodies forever 2. OR is going to be something like porting our brain, “mind” to a computer/robot?

17:15 – Most likely strategies to increase lifespan

19:25 – Ryan Hoover asks – Ask about the ethics of longevity. Jack J. Fernandes asks – Do people actually want to live longer?

21:20 – Mica asks – How would immortality change society? Wouldn’t we become more complacent? Since we have “forever” to do things wouldn’t that diminish our rate of innovation? And since less new individuals are being created we would have access to less new ideas. We would just stop creating new Newtons, Einsteins, Mozarts…

24:30 – Cognitive enhancement

25:30 – Daily habits

33:50 – Tech environment changes in the past 5-10 years

39:00 – What percentage of people in labs want to start companies?

41:15 – Pioneer

43:35 – Confidence

45:30 – Podcasting

48:50 – Choosing media to consume

51:55 – Sam Betesh asks – The last thing that led to a step function change in average life span was germ theory. What new areas of research might provide the next step function change?

54:45 – Extending fertility windows

57:00 – Jason Choi asks – What % of longevity is attributable to lifestyle choices vs genetics and the progress of technology in influencing both.

58:15 – Fatih asks – is blood transfusion a thing or just a hoax

1:00:20 – Rapamycin

1:02:05 – Testosterone

1:04:15 – Chris asks – Aubrey De Grey, IIRC, mentioned a number of times that we might, in the future, replace organs and tissues with new organic ones before they fail. Is this actually a reasonable idea, or is it more likely that we’ll replace them with synthetic ones, if we replace them at all?

1:05:45 – Mica asks – Laura did a “cookie diet” for one month. Why did you do it? How did you feel? Doesn’t it go against all the research on longevity? 😉

1:07:45 – Is Laura actually not doing anything strange in her diet?

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Transcript

Craig Cannon [00:00:00] – Hey how’s it going? This is Craig Cannon and you’re listening to Y Combinator’s podcast. Today’s episode is with Laura Deming. Laura’s a partner at the Longevity Fund. They invest in companies that will allow us to live longer, and healthier lives. You can learn more about them at longevity.vc. Laura’s on Twitter, @LauraDeming. All right, here we go. Laura, why now in terms of longevity? What’s happened to make you raise a fund and start investing in researching companies?

Laura Deming [00:00:30] – This is an insanely important part of the story because if you were Aristotle and you were trying to start a longevity fund, you would have a terrible time! It’d be like you have the worst idea and so timing is super important. Why now, for the first time in 2,000, 3,000 years is it the correct time to work on longevity? To us, a lot of that comes back to tooling and what’s available for us to use. Prior to the 1900’s, if you wanted to impact biology, maybe you should’ve been a physicist, worked on optics, helped make the first microscope and like Robert Hook, a physicist, discovers the cell. There’s so much that comes from physics and other disciplines into biology to push it forward. But thenin the 190 0’s, something kind of fascinating happens which is that, for the first time, there’s kind of this acceleration of tooling. X rays, NMR, all these things. The cathode ray tube discovered. Mass spectrometry, by this guy trying to find a massive electron, which is so cool. All of these physics tools are coming online, but then also more biology driven tools. We can get into this more specifically maybe at a later time but, what’s excited us is just seeing the tools available to characterize life become available for the first time ever. For all millennia, you had Darwin and Mendel talk about genetics, and there was no knowledge of what was actually going on at the ground truth level.

Laura Deming [00:02:01] – In 1953, for the first time, you have the link between molecular biology and we’re looking with microscopes and genetics and this sort of concept of heredity. Which is just super exciting.

Craig Cannon [00:02:11] – What caused you to jump in?

Laura Deming [00:02:13] – Well I mean A, I was born at like a very lucky time, right? Which you always have to be cautious or I guess a little bit concerned if you feel that about yourself. Why now, should it really be the lucky time? As a kid I, A, just had a lot of relatives that were aging and that was very striking, but also, really wanted to solve cancer, and I was, I remember talking to my dad about this like “Oh, I want to solve cancer.” And he was like “Well, cancer’s a subset of aging. So if you want to solve cancer,” he was just like, “solve aging, and it takes care of

Laura Deming [00:02:43] – all these other things, as well.” That coupled with my grandma, that just made sense to me as a kid. I was like, “Okay, well, guess I’ll go solve aging then… That’s the biggest problem.”

Craig Cannon [00:02:53] – Because cancer is not the number one cause of death in the U.S., right? It’s heart disease, something like that?

Laura Deming [00:02:57] – Right, well if you look at all the age related diseases, past a certain point, are driving the majority of natural death so to speak. Once we got rid of infectious disease, it really became the case, aging which wasn’t previously necessarily the biggest issue, rose to the forefront. It sort of just made sense to a small child that that was important.

Craig Cannon [00:03:19] – Why raise a fund rather than just go for curing cancer?

Laura Deming [00:03:24] – The thinking at the time was possibly in a good way, like, emperor has no clothes, should we be simplistic? You have to understand, I was at MIT, and I was like a Sophomore. I was also sixteen and I had like maybe 1,000 dollars in my bank account. Knowledge about the financial industry… relatively low. My dad had been a public investor so I knew a lot about the idea of investing in things, like that was a generally good thing to do. I’d worked in aging labs, for maybe four years. The striking thing was just there was just no money to make drugs. It’s kind of hard when you’re in a lab, you just have no idea what’s going on in the outside world.

Craig Cannon [00:04:00] – I would ask venture capitalists. I would call up a few in the phone book and a few responded and had these random conversations. And just be like, “You know, I’m just curious. I’m a student, can you tell me more about how this industry works? Are you funding aging therapeutics?” None of them had heard of aging therapeutics. They were kind of like, “Asian therapeutics? What did you say?” That was just very striking, that something that I personally believed, on the technology, not just from a mission perspective, on the technology side was super exciting, was generally not really looked at a lot by these folks who were supposedly the great translators of technology. It kind of made sense, the first ever mutation found to extend worm lifetime was in 1983. The next was 1993. Really, the field started about 20, 30 years ago.

Laura Deming [00:04:46] – It kind of made sense, if you think about how long it takes for a field to get traction, become known. Okay, there might be less than 100 good labs in this space. Maybe people just haven’t had enough time, on the venture, investment side to understand that this is really cool and important. Then it made sense that you might want to start a fund, if that were the case, to help more drugs get started out of this space.

Craig Cannon [00:05:06] – In other words, the big pharmaceutical companies are not investing in these pilot ideas.

Laura Deming [00:05:11] – They weren’t at the time.

Craig Cannon [00:05:12] – This was five years ago?

Laura Deming [00:05:14] – Seven years ago. Things are really changed. Seven years ago, there were maybe three companies that had been started, that had the aging brand on them. There was zero people interested. Arch ventures, we were one of the few that were taking risks. There was maybe 10 million invested that year, in total, in that space. In the last four years, we’ve had 10 billion plus. We now see 300 companies per year. It’s just really changed. It’s very, very striking. To have watched it go from

Craig Cannon [00:05:38] – Wow!

Laura Deming [00:05:39] – zero to what it is today.

Craig Cannon [00:05:41] – Now it’s totally a trend.

Laura Deming [00:05:43] – Hopefully it sticks around.

Craig Cannon [00:05:44] – You have, not a million, but many questions for you. Top of the list for me, is what you do personally.

Laura Deming [00:05:51] – Ah, yes. This is probably the most common question. All my friends will always say that I answer this terribly, because I come from a semi-scientific background. We like to get to the ground truth of things and it’s just really hard. There’s just a million, if you start reading mouse’s longevity, you will find mouse’s that, say, if you decrease, like they’ve done this experiment where, you take fat, and sugar, and protein, and you decrease the level of each of them, but keep the total calorie intake the same, you can test which component of diet is contributing to longevity. They did a full matrix. They did lifetime studies for each of the different proportions. And what they found from that study in mice was that decreasing protein was the number one thing that increased longevity. from that you might infer that maybe less protein is good. But at the same time, it doesn’t seem… maybe if you work out a lot, that would be different. I have some thesis about what is good, and what is not good. As a scientist, it’s really hard to say that there’s a good, real, hypothesis there.

Laura Deming [00:06:55] – Despite reading probably more papers on this than most people in the world, it really is something where I don’t see things that are extremely clear movers for longevity. On the diet level, obviously, that aren’t confounded by other things.

Craig Cannon [00:07:14] – What’s your diet?

Laura Deming [00:07:16] – I’ve tried a variety of things. Right now, it’s just the bare minimal, like trying to eat low sugar. Personally trying low protein, just because that is somewhat supported by the literature.

Craig Cannon [00:07:31] – Low protein is a gram per kilogram per day?

Laura Deming [00:07:38] – That’s a good question. What is the correct, per person? Also, if you exercise. I actually, once, tried to calculate out if you exercise, how much protein would be required to replenish all of your myosin and actin proteins. It’s kind of fascinating. I think that there might be up to a hundred fold increase in power, in your muscles, where, if they all fired at the same time, you’d get sort of, a lot of power. I don’t have any strong inclinations on diet. I’ve read basically all the studies.

Laura Deming [00:08:08] – Maybe low protein, low sugar, are both feeling, intermittent fasting, seems to be somewhat supported.

Craig Cannon [00:08:14] – Are you doing that?

Laura Deming [00:08:15] – I’ve tried it. It’s hard to maintain if you have a graduating sleep cycle. I wish I had better recommendations for that area.

Craig Cannon [00:08:25] – In terms of supplements? You doing anything?

Laura Deming [00:08:28] – There’s a variety of people working on everything from A and D plus, all the way to Metformin, for the more adventurous. We actually have a secret list at the fund on market drugs and things that we think, based on our body of evidence, might be having an impact on lifespan, and we’re monitoring them. Some of them I personally think would be intriguing to take. We don’t release that list, just because we’re afraid that if we did, and somebody acted on it and it didn’t work out well for them, that’d be a terrible thing to do, to them. We have a secret list of things that we think are interesting.

Laura Deming [00:08:59] – For the A and D plus, though, there’s some evidence of positive effect there. But we haven’t seen with a large increase in lifespan. That would be my one concern, there.

Craig Cannon [00:09:08] – In the worm, and mouse studies, there have been 100% increase in lifespan, right?

Laura Deming [00:09:16] – Worm studies, we’ve gotten up to 10 fold reported, possibly more. That’s by decreasing a gene product, though. That’s kind of like, if you wanted to go and take a gene therapy, or we had such a thing, from birth, possibly that would work, but probably the effect would be a lot smaller. In mice you got about up to a two fold increase, and that was a combination of a mutation, and restricting the total core intake of the mouse.

Craig Cannon [00:09:41] – Down to what, relative?

Laura Deming [00:09:43] – I don’t remember for that study, on average, I think people will do C.R. down to about 30% of normal caloric intake. But it really varies. If you take 40 different, and this is where it gets complicated. You take 40 different, genetically different strains of mice, and you change their diet in the same way, half will live shorter, and half will live longer. I used to, as a kid, I was like, “There’s a simple answer.” And I think that there is. But I think it is a lot more reliant on genetics, and other things, than we’d like to think.

Craig Cannon [00:10:14] – How long have your family members lived?

Laura Deming [00:10:18] – How long have my family members lived?

Craig Cannon [00:10:21] – Your grandparents, great grandparents.

Laura Deming [00:10:23] – Well, my grandma is still going. She’s in her mid 90’s.

Craig Cannon [00:10:25] – Good sign.

Laura Deming [00:10:26] – Yes, exactly. They’ve all lived about age 80 or above, so, you know, hopefully. How about yourself? How long has your family

Craig Cannon [00:10:34] – Ah, not 90. We’ll see how it goes. I need it more’n you.

Laura Deming [00:10:37] – Right, yup. What would you say the number one health hack that you would recommend to your, your audience, would be?

Craig Cannon [00:10:44] – I’ve done a little bit of blood work, so everything is kind of anecdotal and based on feel, but, I was vegetarian for eight years.

Laura Deming [00:10:53] – Oh, interesting!

Craig Cannon [00:10:55] – For environmental reasons, and then I realized, I had developed this entire vocabulary around cheating. For example, if I was traveling, it was cultural meat! It was allowed.

Laura Deming [00:11:08] – That’s funny!

Craig Cannon [00:11:09] – And if I was over at your house, and you made chicken, or something, I’d be like, “Eh whatever. I’ll have it.”

Laura Deming [00:11:13] – I see.

Craig Cannon [00:11:15] – And at the point where it was like, twice a month, I was like, “I’m not vegetarian anymore.’

Laura Deming [00:11:19] – Interesting.

Craig Cannon [00:11:20] – Then I started eating more protein, but really just more eggs. And then I felt a lot better. But really the main thing is sleep, prioritizing that.

Laura Deming [00:11:27] – Yeah, no, that makes sense. I will say that actually one thing that’s interesting on the health front, I think, people have this intuition that when they feel better, that’s a metric for something that’s good for them. I think it’s actually not true. Maybe you want to optimize like, robust, very cheerful life span. In which case, tautologically it is. But most of the time, or a lot of the time, when you C.R. mice, or you do other things like make them live longer, so total number of years increases, they don’t look, kind of like, as happy on a day to day basis. Like, they’re a little bit thinner, little bit more lethargic in some cases. So, I think it’s kind of like, you know, when someone says, “I really feel ?etter because I’m doing X.” I’m always like, “Oh gosh,” like, I wonder if that’s the correct thing. Maybe, maybe not, hard to say.

Craig Cannon [00:12:07] – Well when people talk about health span, in my mind, it’s very correlated to how I feel.

Laura Deming [00:12:10] – Right.

Craig Cannon [00:12:11] – If I was going to do caloric restriction, and every day would suck, for 90 years, I would opt out. I don’t know if there’s a drug, for instance, I know a lot of people who have experimented with Keto and other random diets, and they’re just caffeinated to the gills. It’s low energy.

Laura Deming [00:12:29] – That’s so funny.

Craig Cannon [00:12:30] – That’s one thing you can do.

Laura Deming [00:12:32] – Oh my gosh. Yeah, that’s hilarious. Yeah.

Craig Cannon [00:12:34] – One thing I’ve been curious about. There seems to be relatively limited data on actual humans. How might someone set up a study, is it even possible now, or is everything so regulated?

Laura Deming [00:12:47] – Well, there is a fellow, near Barnsley, who’s working on what’s called, the “Train” Trial, and the point of that is to assay the effects of this drug, Metformin, which is a very old diabetes drug, on markers, or biomarkers of aging, that he has put forward. The cost for that is about 60 million dollars. If people do it, the idea would be that, okay, well, here’s our first pass at testing aging in humans, and so finally we’d have some more data. The way that trial motivated, was there was these large finding that in hundreds of thousands of patients, or, I think, about actually 70 thousand, that population, from a U.K. study, if you looked retrospectively, people who had been taking Metformin for decades they had apparently a little bit better health span. They had less age related disease, the diabetics on this drug, even than their non-diabetic counterparts, who were not taking Metformin. Hard to have studies that have definitive evidence, but that kind of motivated all of this question asking. Could we really nail down in human trials that test Metformin in particular. That said, a lot of biologists will say, “Oh it’s very important, test things in humans”. And of course it is.

Laura Deming [00:13:57] – If we could do that, we would be doing it all over the place. But I think increasingly over the years, and maybe this is because I started out in worm biology, I’m more and more excited about the animal kingdom. The animal kingdom is absolutely awesome. We have one company in our current portfolio that’s working on this, and their amazing fauna. It’s, there’s such a diversity of phenotypes. And how can we learn from other animals, opposed to just, like, our lowly selves. Because, for example, there’s naked mole rats, and rats. Where, naked mole rats are pushing 30 on life span. We have no idea how long they live. Their mortality rate at 30’s just not going up. We’re just watching these guys, waiting for them to start dying. And then rats, which have very similar physiology, live maybe like, three to four years. What on earth is different between these two animals, right?

Laura Deming [00:14:42] – That’s just absolutely fascinating. It’s also important, because, a lot of physicists and mathematicians, and I used to be this way, like, we’re always worried, What if there’s inherent limitation on the complexity level. What if, given a certain complex system, a certain rate of metabolism, you have to die, because there’s some kind of theory of entropy increasing over time, and must and too complex to really intervene. But then, these animals are basically the same size, have so many other similarities. It would just be very hard to maintain that theory, and also accept this larger picture of longevity.

Craig Cannon [00:15:16] – Absolutely. Someone asked a question that I thought was kind of funny. Yeah, here we go. Mike asks, basically, do you think immortality is going to be achieved by curing all diseases, so in other words, live forever, or, what’s going to happen first? That, or are we just going to upload our consciousness to a computer and live forever that way?

Laura Deming [00:15:34] – That is a question that I used to get very interested in.

Craig Cannon [00:15:43] – Where do you work exactly?

Laura Deming [00:15:47] – The way I think about it, which is not a good answer, but it’s a framework for this question, is I think about biology like a set of tools. You can see this in things that have become available recently, for us to use to effect human health. What I mean by that, is that, prior to the 1900’s, or even just the 1980’s, or maybe the 1930’s. The first time you looked for this marker, if you wanted to make a drug, it was a small molecule. You got a plant, you found something from that was useful or, you put some salve on a wound, which we realize, that’s a bad idea, don’t do that! Not very good for sterility! There were all these things you would do, but then in the 20th century, for the first time, we used proteins, insulin, or antibodies created by our own bodies, or the bodies of the mice that we cloned them in, to treat disease. We actually used something that came from life, to treat a living organism. We now, just in the past three years had landmark approvals in viruses being used to blow up cancer, literally. These are called oncolytic viruses. There’s new drugs using genetically engineered cells. You’ve probably heard of this oncology phenomenon. Also, stem cells being used. The final frontier of all of that, use of biology’s own system to do cool stuff is the brain understanding that system. To lead up to that you will do so many things, that we will get there at the same time, right? So, that’s like the final frontier

Laura Deming [00:17:13] – and we saw that along the way we’ve done enough work on the other tooling fronts, that we get to a… Maybe we don’t solve life span itself, but longevity’s impacted the work up to that time.

Craig Cannon [00:17:25] – Right, exactly. do you sense that there’s a strong signal at this point, as to what might be the way that we, a bunch of people asked these questions, increasing life span by like 20%? If you had to put money on it, obviously, you literally put money on it.

Laura Deming [00:17:41] – Yes.

Craig Cannon [00:17:42] – What would be the most likely thing to take off?

Laura Deming [00:17:45] – The most likely thing?

Craig Cannon [00:17:47] – In the next, I don’t know, 50 years.

Laura Deming [00:17:49] – Here’s how we think about it. We have extremely strong confidence that it’s possible to impact life span between three months, to maybe 10 years and obviously there are different probabilities, with what we have to, in fact, we’re pretty certain that there are some things in the clinic already, or on the market, that with some probability are impacting life span.

Craig Cannon [00:18:11] – Right, okay.

Laura Deming [00:18:12] – Life span seems to be very malleable to a small degree. The larger question is A, how many of those can you put together, to get the maximum impact from that first wave, and then B, our thesis is that none of those things will be sufficient, on their own, to result in an engineered lifespan. You have this first wave of things that kind of work, but they’re kind of limited. They’re maybe at like 60%. And that’s like the max. Then the question is, how can you go above that? We think it all comes back to tooling. So that’s where, I don’t know if we’re Aristotle, or if we’re more like Newton, or in a best case scenario, we’re like Einstein, or someone today in the realm of physics, in terms of going to the moon. And where you tried to go to the moon in 1600’s, it’d be a little bit hard, more recently, a little bit easier. That’s where we have some hope and optimism, but we’re not as confident that there are things today that we’d point to, to say, “That’s going to’ result in unbounded, engineered ability to impact longevity.” And that’s why we also really care about tools, when we think about investing in this space. Not just the first wave of awesome therapies that’ll be available sooner, but, maybe aren’t just like kind of engineer able.

Craig Cannon [00:19:16] – Right, so you’re kind of hedging, if this is still a foundational stage.

Laura Deming [00:19:19] – Right, exactly. I think, we’d love to think that it is.

Craig Cannon [00:19:21] – Yeah, of course! Yeah, yeah, yeah.

Laura Deming [00:19:23] – But, 1953, my argument for foundation stage would be like, this is the first time, ever, in history that we have the link between genetics and microbiology. That happened in 1953, that’s pretty land mark, maybe it’s been 70 years, so you’re like, “Well what happened in 70 years? Couldn’t it just have happened right after 1953?” But I think that’d be the argument for that’s why today makes sense from an engineering perspective.

Craig Cannon [00:19:40] – Ethically, Ryan Hoover asked about the ethics of longevity. Another, Jack Fernandez asked if people want to actually want to live longer? Do you have strong opinions on this, or are you kind of stepping back?

Laura Deming [00:19:56] – We get asked about this all the time. It was funny because when I started the fund, I never thought that people would ask those questions.

Craig Cannon [00:20:04] – You thought it was assumed?

Laura Deming [00:20:05] – Well because the reason we started the fund was to cure things like cancer, and Alzheimer’s. From our perspective, it was a whole, you would never ask, is it good to cure cancer? No one would ever ask that question, that I’ve heard of. Or maybe some people would! But then we realized, when people think longevity, they think about it as different than those things. From our perspective, I think it makes sense to cure these diseases, if we can. We definitely want to do that. And so, we would never deviate from our mission. I think from a broader scale, it’s kind of’ like, two camps of like, do you want to be Malthusian in your thinking of the world as like a bounded place, it’s really limited resources. Or, kind of like David Deutschian, like, you know like, we’re on, you know, spaceship Earth, but, no, we’re not actually. Let’s go and explore the cosmos, and unlimited resources, and energy is in all matter. I think there’s, from a philosophical standpoint, I’m more in the latter camp.

Laura Deming [00:20:57] – I just like that kind of viewpoint a little bit better. The rationale for longevity really was, “Let’s cure diseases. How do you do that? You work on aging.”

Craig Cannon [00:21:06] – Maybe there are multiple universes where we live forever. I’m trying to get David on the podcast. I met him one time and he talked about it.

Laura Deming [00:21:15] – Really!

Craig Cannon [00:21:15] – Yeah, yeah, yeah, yeah.

Laura Deming [00:21:16] – Would you have to go to him, and his house?

Craig Cannon [00:21:18] – That’s what I did when I met him.

Laura Deming [00:21:20] – That would be the best trip you ever had.

Craig Cannon [00:21:23] – He did one with Sam Harris that was kind of cool.

Laura Deming [00:21:26] – Oh my gosh.

Craig Cannon [00:21:27] – But really, in terms of having an actual opinion on this. There is a cool one on the Ethics, Micah asked, “How would immortality change society? Wouldn’t be become more complacent, since we have forever to do things? Wouldn’t that diminish our rate of innovation? And since less new individuals are being created, we would have less access to new ideas.” In other words, there are fewer Newtons, fewer Einsteins. And this is like, one of the basic income arguments.

Laura Deming [00:21:56] – Right.

Craig Cannon [00:21:57] – You allow for these people to succeed.

Laura Deming [00:21:59] – Well, so, I think there are two implicit assumptions there. One is that we understand how people are motivated. Their motivation stems from this feeling that they will die. Number two is this idea that people have an innate rate of loss of new ideas with age, and a loss of openness. And so I think, you know, addressing both of those, on the first point, and I think they’re kind of valid questions, I don’t think that that’s true, personally. Okay, I don’t think I’m motivated to do things because I know that I’m going to die. I think that, perhaps everyone else is, and this is kind of a personal thing, but again, I’m motivated by many things, like curiosity, competition, personal growth, wanting to be better next year, than was today, a sense of mission, and importance. It’s important to go do certain things. If you ask most people, maybe they’d have different answers, but I’m curious if death really is the core motivator to do things, for everyone in the world. That’s one thing. It might result in fewer people wanting to go to war. Which might be problematic if you want more war and more soldiers. Or not, if you would like less war. But I think for that part, I don’t agree

Laura Deming [00:23:10] – that we really understand that the core motivation for everyone on this planet, and that that is, by it’s definition, the fear of death. The other thing that’s interesting, to the second points, the question of loss as this age. There is a lot of cognitive change with age. Which is very fascinating, right? Biologically, you do change. Part of what we really want to do, is impact aging, but a large part of it, we can just make a cognitive enhancer, so you were like sharp until you’re nine, and then you dropped, that would be an awesome product in and of itself. Just cognitive enhancement, alone, would be great. People actually kind of under counting, the value of potentially, if you’re a Newton, absolutely brilliant, and you helped develop a field, and maintain your 20 year old openness and fluidity,

Craig Cannon [00:23:58] – For 100 years.

Laura Deming [00:23:59] – All the way through to age 90, What kind of insane ideas would Newton be coming up with at age 90? With that kind of openness. The counter argument there is, well he would just go and do alchemy, so then you have young Newton being great, and old Newton doing alchemy. The counter argument is, well maybe alchemy caused the decline in thinking because he was sniffing too much mercury. I won’t counter argue!

Craig Cannon [00:24:17] – You almost won an argument for outsider scientists, who don’t get discovered until they die. And then they have 100 years of portfolio.

Laura Deming [00:24:25] – Right! And there are also, so many people, like some incredible physicists at Stanford, who are still amazing, and coming up with extremely novel ideas. Hawking publishing on black holes and entropy, his final paper, on this completely novel fascinating field. Was he declining? Would we need Hawking to step aside, for the younger generation, can’t we have both? I guess would be the question.

Craig Cannon [00:24:48] – Interesting. Would you be a proponent of giving the entire, similar to fluoride in the water, putting Provigil in the water?

Laura Deming [00:24:56] – I’m never a fan of things that don’t involve individual choice. Anything that would be coercive, or enforcement, then no. If everyone signed up for it, then I do think there’s all this fascinating work on cognitive enhancement, just starting to come out today. We used to have a lot of companies that were super excited about the making your neurons make synapses more essentially. Increasing their rate of division or hypothetically… That’s part of longevity. If we just had a pill for cognitive enhancement that in and of itself would be absolutely wonderful.

Craig Cannon [00:25:32] – Everything I’ve tried, it works. There are sometimes where you get this feeling that you’re really good at, you’re crushing email and your just sweating the whole day.

Laura Deming [00:25:50] – Have you ever read this book, Daily Habits?

Craig Cannon [00:25:52] – No.

Laura Deming [00:25:53] – I think you might like it. It’s the daily habits of mostly writers and artists. It’s super fascinating because it details how they live their life. It’s extremely variable, but the most common thing is they all wake up and go to sleep, like, they have a very set routine. Of when they wake up to work, and go to sleep.

Craig Cannon [00:26:07] – I’m already on that cycle. A thing I have found is that my mornings are much more valuable than my evenings. Especially in the middle of the day, I’m kind of useless. I just work out at two in the afternoon.

Laura Deming [00:26:23] – I’m curious why that is. It’s either biological or psychological. You get too much loaded into your brain, and you don’t want to think, or, it’d be really fascinating if sleep played a key role there. Sort of like sleep does something biologically and perhaps psychologically, that somehow, induces an optimal state, right when you wake up.

Craig Cannon [00:26:41] – Have you tried it? Sleeping in the middle of the day and then just getting back to work?

Laura Deming [00:26:44] – I have not, but that’s an interesting idea. I’m curious what that would do.

Craig Cannon [00:26:48] – I’m so curious about cognitive enhancement. We did a podcast with Rosalind Watts, who is at Imperial, about psychedelics.

Laura Deming [00:26:56] – Oh, that’s awesome!

Craig Cannon [00:26:57] – We’re, awesome. It’s very similar. Actually, her research with Robin Carhart Harris at Imperial, is in Michael Pollan’s book.

Laura Deming [00:27:07] – Oh, Interesting.

Craig Cannon [00:27:08] – Did you read that?

Laura Deming [00:27:09] – No, I’ve heard so much about it, though.

Craig Cannon [00:27:11] – Yeah, it’s really great. But it’s kind of like cognitive enhancement in a very broad sense. In terms of trying to break you out of your old habits and have more confidence. Increase openness and…

Laura Deming [00:27:21] – Yeah, exactly. Are you taking anything in the nootropic sense?

Craig Cannon [00:27:28] – Entropic sense? Consistently?

Laura Deming [00:27:30] – No, I don’t even do caffeine. Because the general thought is like try to wean yourself off of everything. If you can perform great there, then perhaps some day there’ll be a safe drug that comes on the market, that’s worth trying. I also like Marcus Aurelius’ stoicism, none of the unnecessary things. Maybe that’s misapplication of that philosophy, now that I think about it.

Craig Cannon [00:27:49] – Some part of that just makes me angry.

Laura Deming [00:27:52] – Really?

Craig Cannon [00:27:53] – I’m a dichotomy. It’s all stretched apart, because, I’m very much a creature of habit. That being said, like caloric restriction, not having a beer with my friends.

Laura Deming [00:28:10] – Oh, I see, yeah.

Craig Cannon [00:28:11] – I don’t, I’m not doing it. I’d rather work out an extra time. But then, some people say that’s bad for your heart.

Laura Deming [00:28:22] – Right, you can’t win! You can’t win.

Craig Cannon [00:28:24] – I feel like in some ways it’s like the devil I know and I just avoid other vices like texting while driving and smoking.

Laura Deming [00:28:36] – That’s interesting. What is the thing that you do that you’re the most proud of? The habit that is the hardest for you to maintain, that you nevertheless are quite happy to be able to do?

Craig Cannon [00:28:51] – Exercise is no problem because I go crazy without doing it.

Laura Deming [00:28:57] – Right.

Craig Cannon [00:28:59] – What’s consistently the hardest to maintain is giving energy to the side projects that are creatively demanding.

Laura Deming [00:29:09] – Oh, that’s interesting.

Craig Cannon [00:29:12] – Because I, this is what I didn’t expect. I used to work for myself, and now I work at YC, obviously, and there are, obviously. You have so much energy, in the day, and obviously you can push harder, and get work done, and be more disciplined, but I found that there are certain side project ideas that are just kind of too much, to even think about.

Laura Deming [00:29:38] – Oh, interesting.

Craig Cannon [00:29:39] – When I make progress on that, I’m very happy with myself, because the side projects that are like, you know I’ve made little SaSS tools, and stuff, and that’s cool. It’s definitely not the hardest thing.

Laura Deming [00:29:53] – What allows you to make progress on those projects?

Craig Cannon [00:29:59] – Just internal motivation, wanting to do it. What’s always helpful is just to imagine yourself in 10 years and look back.

Laura Deming [00:30:08] – Oh, interesting!

Craig Cannon [00:30:10] – Then just use that as a metric for what you want to do. Would you be proud of yourself for having done that?

Laura Deming [00:30:15] – That seems somewhat like the of when you’re 60 and you look back on your life. That’s interesting.

Craig Cannon [00:30:22] – But then, but dude it’s like, who’s to say what’s going to lead to the next thing that’s great? Before we did the podcast, I was talking about working at The Onion, right?

Laura Deming [00:30:34] – Right.

Craig Cannon [00:30:35] – Now I’m here. You’re like, that’s not a standard trajectory.

Laura Deming [00:30:38] – Right.

Craig Cannon [00:30:39] – You can’t really say, authoritatively, the best way to spend your time is x. When I was a kid, someone said to me, before you start working on something, think about what winning looks like and that’s kind of a framework for projects for me.

Laura Deming [00:31:00] – Oh that’s interesting.

Craig Cannon [00:31:02] – But I don’t know. It’s just a personal thing.

Laura Deming [00:31:05] – What other hacks and motivations do you have in your arsenal?

Craig Cannon [00:31:14] – I just don’t spend time with people that annoy me or stress me out.

Laura Deming [00:31:17] – Okay, yeah.

Craig Cannon [00:31:18] – That’s a positive thing. I am never busy, but I am fine using that excuse.

Laura Deming [00:31:27] – Oh, you’re never busy?

Craig Cannon [00:31:29] – I always have time for my friends, and the things that I really want to do. I just cut everything else out. I don’t know, how about you?

Laura Deming [00:31:38] – I need to try and keep the baseline pretty low, like, I think you can control your output, but you can’t really control how the world responds to it. It’s kind of like, if you’re just like, all right, I’ve had a good output, then that’s great. However the world responds, you can’t control it, but being really happy when you do something you can control is probably the biggest mental hack because usually you just can’t control it.

Craig Cannon [00:32:08] – It’s so hard because, you’re still pretty young. How old are you?

Laura Deming [00:32:11] – 24.

Craig Cannon [00:32:12] – I remember when I just moved out here…

Laura Deming [00:32:16] – How old were you then?

Craig Cannon [00:32:17] – 23, 24, something like that.

Laura Deming [00:32:22] – Oh, so you had just come out of college, or?

Craig Cannon [00:32:25] – What happened was, I was in New York for college, and then I lived there for like a couple years afterwards, and my girlfriend and I split up, and I was like, I had always wanted to live in California, and New York was just like Argh! Just like, grinding at me! So, I just moved out here.

Laura Deming [00:32:41] – Oh, interesting, wow.

Craig Cannon [00:32:42] – Which has been cool.

Laura Deming [00:32:45] – Wait, did you have a job or something or you just moved out?

Craig Cannon [00:32:48] – The Onion moved from New York to Chicago and almost everyone left. I started a company with my friends and we were doing these hackathons where developers and comedians made stuff together.

Laura Deming [00:32:59] – Okay, that’s cool.

Craig Cannon [00:33:01] – It was a total not startup, total small business. Super fun. We did one with Twitter. I moved out here for that, thinking I would be out here for months, and now it’s like, whatever, six years later.

Laura Deming [00:33:14] – But what about California was so different for you that you had to stay here?

Craig Cannon [00:33:19] – Well I love doing outdoor stuff for sure.

Laura Deming [00:33:22] – Oh, okay.

Craig Cannon [00:33:23] – But it’s a trade, I don’t know. Everyone wants to talk shit both ways, and it’s totally a trade. Culturally, it’s not the same thing as New York, but then, if you’re working in tech, or entertainment stuff, I mean, New York is kind of a mix, but there’s L.A. It just seems so much more professional. Not in the polished sense. But like, everyone is, or like most people are, here. And that’s cool. That was cool to me. Going to these coffee shops, and seeing this person that I had only seen on the internet before, and I was like, man, all this shit’s happening here!

Laura Deming [00:33:58] – That’s interesting!

Craig Cannon [00:33:59] – But, I don’t know.

Laura Deming [00:34:05] – How do you think things have changed in the last seven years, or like, has it been seven years for you?

Craig Cannon [00:34:09] – Something like that yeah.

Laura Deming [00:34:10] – What has been the biggest thing that’s changed, either both positively, or negatively, or neutrally?

Craig Cannon [00:34:15] – In myself, or?

Laura Deming [00:34:16] – In the environment that you’ve seen. From when you first got here.

Craig Cannon [00:34:20] – Oh, that’s easy, that’s super easy. Tech is completely vilified. That’s been the biggest shift.

Laura Deming [00:34:25] – Oh, interesting.

Craig Cannon [00:34:26] – Yeah, if it’s not this next election, it’s the one afterwards. Tech is the evil thing.

Laura Deming [00:34:32] – Interesting. And did you see what drove that?

Craig Cannon [00:34:41] – Well in some ways it’s an incredible amount of wealth being accrued to a small amount of people. They’re young, and I think their amount of power is just off putting to so many folks.

Laura Deming [00:34:53] – Oh, I see, just kind of like.

Craig Cannon [00:34:54] – Obviously with the Facebook thing, and that kind of thing.

Laura Deming [00:34:58] – the person to vilify, and

Craig Cannon [00:34:59] – It just feels like the new banker to me.

Laura Deming [00:35:02] – Ah, yes.

Craig Cannon [00:35:03] – And that’s the, that’s been the shift.

Laura Deming [00:35:05] – So not a great precedent, in general.

Craig Cannon [00:35:07] – Have you noticed anything?

Laura Deming [00:35:10] – In Bio, it’s just no one’s paying attention to Bio. We’re just all the way over here, kind of like, working on things that take a long time, and are very hard and expensive, so people are like, “Oh! Yeah, they’re still over there, still working on drugs.” I don’t think, as much. Really there are very few billionaires in Biotech. That was something that was very shocking to me when I first came out. I was looking for people who were amazing, and also had made a lot of capital, in Biotech because those are the people who would be successful, and know how to build business as well. Least that was my thought. There were very few of them. A lot of them were in VC, who had invested in these companies. Where are the founders not getting the capital, how does that equation work? And then I think, one of them was a former salesman. It was like, the most inform I had ever had about sales, he was just like, because I was trying to understand how do you sell a business, or an idea. From MIT it’s complicated. We had like, textbook about it, and he was like, “You just sit the person down, and tell them what to do.” I was like, “Okay.” Now I think I understand how this whole area of life, how to communicate, a little bit better than I did previously.

Craig Cannon [00:36:15] – That’s so funny. I really hope more of these companies, they are popping up already. We’ve seen longevity, biotech, and if there is any kind of lull in the ecosystem, it’s just going to be fertile ground. There’s been historically a lack of founding different companies. All of the sudden the environment has changed to make it more likely to happen like the next couple of years. But it’s just so striking. It really is different when you have, because if you look at the wealth created in tech, and in biotech, you really see the distribution going so much more to venture capital, I think with the founders. That’s been like a really weird thing to observe on first coming here. Why is that the case?

Craig Cannon [00:36:54] – Do you have different terms than normal VC funds?

Laura Deming [00:36:57] – Well, for our funds?

Craig Cannon [00:36:58] – f that’s a strong opinion you have, what are your terms?

Laura Deming [00:37:04] – We have like, H1, so, you know, similar to, what you folks are working on, that’s founder driven, that’s like, you know, sort of trying to give people a leg up, and promote as the founder starts the company, and not try to replace them. I guess like some other firms. Which I think is a fair strategy if that’s been your bulwark for decades. But I think marketers would say it’s similar to what’s happened in software. Where you had this first wave of professional managers, you swing back to technologists, you swing back to the middle, now we’d like some more managers, please, but still, technologists are running the show, and I think in bio, we might be midway through that. We’ve had the managers period for a long time. We’ve might have more technologists. And then maybe swing back to the middle. That’s like a pretty simple pattern, actually. Who knows what will really happen in the future?

Craig Cannon [00:37:51] – Yeah, because the, that’s interesting. If it’s a trailing thing from software, because, you prob’ly know this. Yeah, so, what’s happened now, is, maybe 10 years ago, or when YC started, it was incredibly rare for you to be able to just pitch an idea, to get money.

Laura Deming [00:38:05] – Exactly, yes.

Craig Cannon [00:38:06] – Now, you can easily do that. But, more importantly, I hear crazy numbers, from people leaving college, and going to work at Facebook.

Laura Deming [00:38:14] – Yeah, right.

Craig Cannon [00:38:15] – Or big companies. I think that’s probably, over all, bad for the ecosystem. Because it encourages this extreme risk aversion.

Laura Deming [00:38:22] – Right.

Craig Cannon [00:38:23] – The likelihood of lifestyle inflation, and never starting something is high.

Laura Deming [00:38:29] – But think about, so, what enabled YC, right? AWS had, from the outside, a huge part of it. The first ever ability, driven by tooling…

Craig Cannon [00:38:39] – That’s a good point.

Laura Deming [00:38:40] – To kind of spin something up really cheaply. And I think in bio, it’s like, whenever anyone talks to us, there really was this point where, you know, drop in cost of sequencing has been occurring over the past 18 years. But really, up until the past three or four years, you could not get 1,000 genome. Right? Like, that is a recent phenomenon. And so, one argument would be, look at Illumina’s revenues, today, it’s absolutely crazy how similar they are to Intel’s revenues, right in the 1970’s. The parallel there is like, this is between like, a friend of mine, and me, to notice this, there’s this really interesting parallel between the Nabla Technology that we see, in one segment, And what’s happening in bio today. And who knows what’ll happen in the future? But there is an interesting parallel there.

Craig Cannon [00:39:21] – Do you think there are people in labs well, actually, what percentage of people working in labs do you think want to’ start companies?

Laura Deming [00:39:30] – This is the fascinating thing. We were curious, if you look at the amount of funding that’s available on the venture side to go into biotech in the past couple of years, it’s insane, it’s double, triple, in the last couple years, alone. But the number of companies funded has stayed fairly constant. And so we’re just looking at this like, “What the heck is happening here?” What’s happening is, on the top end, the median hasn’t even changed. It’s like the top end of the top quota companies are getting more capital per company. All this capital has to come from LPs, because you’ve seen the NASDAQ biotech index, go from stagnant, up until 2011, to monotonically increasing, although there was definitely a small dip, and then, it’s like, where do you put all this capital? There are no more companies to invest in. We were like why weren’t people starting companies? We went and talked to like 100 grad students, and Post Docs, and then answer they gave us was absolutely striking. It was like most of them, so maybe 10% were worried about reputation risk. They didn’t want to leave, fail, and then go back. 80% had never thought about the idea of starting a company. They just were not aware there was a possibility.

Laura Deming [00:40:31] – You could argue, maybe they’re not entrepreneurial. But, if you think about, in the 80’s, or the 90’s, would you have gone as a CS student at Stanford, and started something, maybe. But maybe you’d have a lot higher of a barrier, or bar to doing that, right? I think that’s part of why YC started to make that process easier. And so I think, really what it is, it’s just a lack of education. And availability of options to these people. Which makes you so angry, right? You should never be forced, or convinced to do something that you don’t want to, or that’s not good for you. You should be aware of your options. How are all these smart people not aware of all the possibilities that are out there for them?

Craig Cannon [00:41:05] – The saddest/funniest one I’ve heard, is when someone, often in like, a hard science lab or background, they learn about YC, and think that we’re just giving them loans. And they’re like, “Oh, no! I could never do that!” Yeah! Which is like, if you had no exposure to this,

Laura Deming [00:41:25] – Oh that’s so crazy.

Craig Cannon [00:41:26] – why wouldn’t you think that? All of these myths exist. But I think the education thing is a good point. For the most part, people don’t even know.

Laura Deming [00:41:35] – That’s absolutely crazy.

Craig Cannon [00:41:36] – You should talk about your, you have so many questions, but you should also maybe mention your project with, Daniel. Because that’s relevant.

Laura Deming [00:41:44] – Yes! Yes, yeah, so. Super excited. My friend, Daniel Gross started this really, really awesome project called Pioneer. What Pioneer is, is it’s trying to find lost Einsteins of the world. Which I think is an awesome tagline. Danny has a fascinating background in that, he was on track to join the Israeli Army, and then, uploaded an application to YC, and, basically, his whole life changed, after one flight out here, and a meeting with Paul Graham, he’s obviously and incredibly successful person, but would he have had the same chance, if not for the luck, I think his Dad forwarded him an article about YC, like that was how he found out about it, right?

Craig Cannon [00:42:25] – Really? I don’t know. That’s great!

Laura Deming [00:42:28] – I think that’s the one thing he mentioned. It was like this coincidence that drove his journey. The question is how many people are there out there, that this small intervention could drastically have a different life course. Pioneer.app is this place where if you’re anybody in the world, and you have a project you want to’ work on, you can apply. And it can be anything. Anywhere from, “I want to have more of my high school friends do science stuff,” all the way through to, “I’m 80, and I finally want to’ write my novel.” And there’s this thing called the Pioneer Tournament, where people work for about 30 days, do their projects, the community votes on their most favorite people. And based on that, at the end, a set of people are selected to be flown to San Francisco. You receive about a 5,000 dollar grant, and they join the Pioneer community. Which is this set of really ambitious outsiders trying to change the world. And, so, I resonate with it because, my personal story was coming from New Zealand, at age 12, based on a random email I sent to a professor here, and it was the first thing I’d ever sent to someone who was not my family member, and she responded. But if she hadn’t responded, and that luck hadn’t occurred, where would I be? I have no idea.

Laura Deming [00:43:34] – That’s why I think Pioneer’s so exciting. Because it might help a lot, everyone listening, you should definitely, definitely apply. Pioneer.app. I think it unlocks so much potential. Everyone in the world who could be doing awesome things.

Craig Cannon [00:43:46] – I think it’s so cool. Just enabling people to have the confidence thing has been the biggest surprise for me at YC.

Laura Deming [00:43:54] – Oh, interesting.

Craig Cannon [00:43:55] – I think a huge, unspoken part of why YC is successful, is that it gives people the confidence to do their thing.

Laura Deming [00:44:02] – Right.

Craig Cannon [00:44:03] – They’re often, I mean, sometimes it’s insider, like tracked, like, “I went to Stanford,” whatever. But sometimes it’s total outsider people, and it works out. Without systems that give people that little extra push, a lot of people will never do it.

Laura Deming [00:44:19] – Ah, interesting. It is counterintuitive, yeah.

Craig Cannon [00:44:22] – It’s crazy. Because I do these office hours occasionally with people who are interested in applying, and they’re awesome, they’re great. All it takes is that one meeting where you’re like, “You’re good enough. You can do it.” That’s it and then they apply. It’s crazy.

Laura Deming [00:44:41] – Interesting. One of the fascinating things that Danny’s going to’ run into is how do you give that, how do you scale that feeling of transmitting confidence? It’s non trivial.

Craig Cannon [00:45:00] – Well you asked me about podcasts before we started, right?

Laura Deming [00:45:03] – Oh, okay.

Craig Cannon [00:45:04] – And so this is like a crazy side effect of podcasting. Because it makes you feel like you know someone really well. But the reality is, you kind of do. That relationship of someone as like, whatever, friend, or mentor, or whatever, is enough to be like, “Oh, I kind of’ get this. I can be myself with them and I can just express whatever I want to do.” But then there are totally weird elements for me. I’ll be in the bathroom at Demo Day, And someone will tap me on the back, and be like, “Oh, man, I liked your podcast!” It’s like, “Cool, not now!”

Laura Deming [00:45:49] – That’s so funny. Do people feel like they know you from hearing so many of your conversations with others and how you think about the world? Because you said that one thing you find fascinating is how other people think about the world. But I guess that the way you ask questions must give some information about how you build models or view systems.

Craig Cannon [00:46:04] – Or how stupid I am. I don’t talk a ton about myself. People get the sense. I was actually talking to my friend about this, this morning. How am I different on the podcast versus in real life?

Laura Deming [00:46:26] – Oh, interesting.

Craig Cannon [00:46:28] – There’s going to be some dissonance there.

Laura Deming [00:46:31] – Right.

Craig Cannon [00:46:33] – I’m curious about how to best merge the two. I haven’t figured it out yet. Because I actually don’t know what the gap is.

Laura Deming [00:46:40] – So you don’t know what your podcast

Craig Cannon [00:46:42] – I was about to text him and I didn’t.

Laura Deming [00:46:45] – Huh. You seem pretty, like, on the surface, similar. But I guess it would be hard to know without a long period of

Craig Cannon [00:46:55] – Oh, you listened to it before?

Laura Deming [00:46:56] – No, I the, first we had a conversation before we started.

Craig Cannon [00:47:00] – Oh, right, yeah.

Laura Deming [00:47:01] – I guess it’s basically the same thing, maybe. Huh, interesting. It’d be better if you were more like the person that you, yeah, what authenticity would bring that like you don’t have now? I’m kind of’ curious.

Craig Cannon [00:47:21] – In some ways, I’m just selfishly interested in making it something that feels more like me.

Laura Deming [00:47:29] – Ah, I see.

Craig Cannon [00:47:30] – It’s my thing. You’re always curious about gains. What could make that show better? When I think about the podcasts that I like. Things like Rogan, stuff like that. I mean, that’s not fringe, but I imagine, and this is again, like projecting, because I’ve never hung out with him. I imagine it’s very close to what hanging out with the person is like. Then, when I watch a podcast of me, sometimes, I can tell that I’m nervous, or not as natural as normal.

Laura Deming [00:48:10] – Do you think it’s the environment? If you made this feel like your living room? It would be slightly different, or?

Craig Cannon [00:48:17] – Yeah, it’s possible. I think one thing that would be beneficial is like hanging out, I mean your great, so it’s very chilled, it’s very easy, but sometimes like hanging out with someone beforehand.

Laura Deming [00:48:32] – Oh, I see. It feels like you have a conversation, and then it just continues into…

Craig Cannon [00:48:36] – My desire to keep it on topic can make it less natural, than it could be, if that makes sense. You know what I mean?

Laura Deming [00:48:51] – Because you always come back to one thing, but maybe that’s not actually the organic way that it would have gone.

Craig Cannon [00:48:57] – Right, because, actually, this will be a good test. Because, I’ll put this one out, and people will be like, “Dude, what the fuck are you doing? Stay on topic with the longevity stuff.” I don’t know. I don’t know, it’s tough. Because, are you a podcast person?

Laura Deming [00:49:12] – I actually am not. I really only do books, and papers. Because podcasts are kind of annoying. You can’t fast forward through them easily, and use your eyes, and figure out, if they were transcribed, then I might read them, but.

Craig Cannon [00:49:28] – YWhich you can, some do. We do, but not everyone.

Laura Deming [00:49:32] – Then I also feel like, I think there’s something about if everyone is listening to the same podcasts, and you go and spend the same amount of time reading the Greeks, like, what Thucydides was thinking, you might have very outdated information that’s not very informed about today, but you might also get, I guess, a similar feel for how somebody was but have them be more correlated, and therefore, ideally, give a better viewpoint than normal.

Craig Cannon [00:50:02] – I think you should. The amount of time I’ve heard people reference Sapiens, or Charlie Munger, I just can’t deal. They’re great, they’re awesome ideas, whatever. But everyone’s consuming the same media.

Laura Deming [00:50:15] – It’s interesting, because if you don’t, and you try to understand it from first principles, which I think is maybe first principles itself being a thing that is often cited as the good thing quite different. One thing most people don’t realize, math and science often are more artistic than they are logical, but everyone’s trying to frame things in a logical process.

Craig Cannon [00:50:37] – Well because it’s a counterintuitive thing. It’s obvious when you say it out loud, to pursue an idea, in math or science, you have to be inspired to pursue it because you don’t know if it’s true beforehand.

Laura Deming [00:50:52] – Exactly! No, it’s so crazy! I think it’s fascinating. Look at Newton. Newton spent, he had this amazing year when he was like 21, he discovers all these things and then he goes into alchemy, and the Bible. And you’re like, what? Where does that come from? But I think part of it is like books where he’s so curious, but I think he also has a little bit of mysticism. This kind of weird aspect of him. It’s like a little bit artistic. We forget that we’re like that. Like, “Oh yeah, scientists are kind of like robots”. But they’re really not.

Craig Cannon [00:51:27] – Definitely not. Definitely not. All right, so, let’s actually get to some of these questions.

Laura Deming [00:51:33] – Please.

Craig Cannon [00:51:35] – Which ones appeal to you? Because we have so many.

Laura Deming [00:51:38] – I think the ones that are factual are good. So, just like the research questions, probably.

Craig Cannon [00:51:44] – All right. Let’s do that. Maybe we should rip through, because I’m genuinely interested in a lot of these, and I read your longevity FAQ, which is awesome. It’s very Tim Urban, Wait But Why, style.

Laura Deming [00:51:59] – Right, yeah.

Craig Cannon [00:52:00] – Maybe it’s the drawings that got me. But that was cool. That must’ve taken a lot of work.

Laura Deming [00:52:08] – Yeah, I was just drawing the axis, and then like, three lines is, it was hard.

Craig Cannon [00:52:15] – Sam Batash asks, “Do you think there’s going to be another step function change in human expansion,

Laura Deming [00:52:23] – Oh, yeah.

Craig Cannon [00:52:24] – since, you know, germ theory? What’s the next one?”

Laura Deming [00:52:27] – I think this is a super fascinating question and time to be alive, because, you know, it’s fascinating. You look back and germ theory was such a huge breakthrough. I think one thing that’s lost, also, is there’s another breakthrough that’s similarly related, which is that life comes from life. Or because for like, all history, we think that there was spontaneous generation of life. Literally up until right about that time. And then Pasteur was like, “Nope, nope, nope. These germs are coming in through the neck of the pipe. It’s not,” And that was just a huge breakthrough. Obviously Darwin’s also very important. I think the thing that we kind of have an intuition of being important, in longevity, that most people are not paying attention to, it’s going to sound way to philosophical, but really when you get into it, I think it’s the important thing, what does it mean to be alive? At what point are you differentiating between the germ line, which is like, your reproductive cells, and the soma, which is like your skin and tissue. Because, there is a immortal line of living things that has been replicating since our first ancestor, right? Transmitted through our germ line. When I have a kid, that kid does not come out and have the same amount of aging that I do, when I have it. It is kind of brand new, right?

Laura Deming [00:53:42] – How the heck does that happen? And how do you fit that, and if you take for example, a bacterium, there are some bacterium that do asymmetrically divide, and possibly have some form of aging, but, do you look at a bacterium and think, that thing is aging? Maybe, maybe not. What is it about multilayerity and our germ line, and the soma, and the differentiation between the two, that’s caused us to evolve or start this aging phenomenon? Given that, is it natural, can we think about how our desire to live longer ourselves, fits into that differentiation. Nature is already solved living forever, on some level, right? On the cell level. What is it about our soma that is so different, and are there any things that we can repurpose and use, for that? That area’s going to be super fascinating. And then, I’m also just broadly in love with the question, what is life, right? That’s so interesting! Schrödinger in the 1930’s, writing these fascinating tracts bringing and others, and so that, and people thinking about at MIT are just absolutely incredible in their work. That’s probably a longer answer. I love these questions. We spend so much time thinking about the practicalities. But the higher level order, like, what will be the actual breakthrough? I think that area’s really interesting.

Craig Cannon [00:54:58] – Sort of a tangent. You mentioned giving birth. Is someone working, I assume someone’s working, are people working on extending fertility windows, if you extend health span? Because that seems like if you could live forever… As a dude, I could just opt out, right? All right, I’m not going to have kids or I’m not going to… In my mind, that’s the real issue. It’s like allocating time. Say you work aggressively until your 30, or 35, or whenever, and then you have kids, like, all of the sudden you have to take care of this thing, or it will die.

Laura Deming [00:55:34] – Right.

Craig Cannon [00:55:35] – Being able to push that until you’re 60 seems really valuable.

Laura Deming [00:55:40] – Yup, so we think that is, sorry, I don’t want to say fascinating so many times. But it really is a fascinating area. Because there are some animals, many in fact, where, you have some octopii that lay their eggs, and then their mouth disappears. And they’re like, sitting on their eggs, and really commit suicide. And if you reverse the glanular action that gives rise to that, they just keep on living.

Craig Cannon [00:56:02] – Whoa.

Laura Deming [00:56:03] – And so it’s like you have programs in essence, all over the animal kingdom, and we are anthropocentric humans, and so we say, “Oh, that doesn’t happen to us”. But, you think about menopause, in a woman. What is that? That is a clocked, acute onset of loss of health, right? Not just fertility, many other things. You get fat distribution, bone loss acutely, at the time of menopause, so many other things get a lot worse, in a clocked fashion. You look at other animals, and go, “Oh but we’re not like that”, but really, are we that different? There are even some hormones that we’re looking into right now that are involved in that process that are super fascinating for longevity. And so, I think that area’s really, really interesting.

Craig Cannon [00:56:38] – I imagine it’s more likely for it to be an artificial womb, than re engineering humans, but maybe that’s inaccurate.

Laura Deming [00:56:46] – The artificial womb area, it’s sort of like, not, if you solve that problem, would it help us solve the longevity problem? But I think there’s actually, there are people that are just thinking about, what is menopause? Right? Because why is it so timed? What is the clock that turns on? If we turned off that clock, would it push backward, is there some kind of natural? There’s some kind of obvious answers for that. But, it really is, how did evolution decide that was the correct time? And so I think that area’s really interesting.

Craig Cannon [00:57:18] – That’s awesome. All right. Jason Choi asks, “What’s the percentage of longevity attributable to lifestyle choices, versus genetics, and the progress of technology in influencing both?”

Laura Deming [00:57:30] – Oh, interesting. So there’s a recent paper that came out, super fascinating, by this guy, Yaniv Ehrlich, in Science, and what it did was, they have a public database of heredity. Basically a family tree. Unfortunately it doesn’t have actual genomic data for each person, but, you have a lot of life span data. So age, birth and death dates, many generations back. You can ask, what is the heritability of longevity? If your parents lived longer, are you also likely to live longer? Prior to that, we had a 25% heritability figure. I think that dropped to about 11%. I could be off on this figure. But I think that paper was about 11%, could be wrong. That’s the current I think that underestimates the potential effects of genetics on longevity, because, do you have mutants that are long lived in the population, no. I think it doesn’t tell you how much genes could be changed to influence longevity. Yeah, but, 11% would be about the current estimate, from the field.

Craig Cannon [00:58:33] – There you go. Fati asks, “Is blood transfusion,” So this is parabiosis,

Laura Deming [00:58:38] – Right, yeah.

Craig Cannon [00:58:40] – “Is it a thing, or just a hoax?”

Laura Deming [00:58:41] – Oh, gosh! No, I avoid the “blood boy” question. The blood boys are like, they follow us around. Everywhere we go, we’re asked about the blood boys. So, one thing that’s fascinating is like, sorry I say fascinating all the time, if you go back and ask, what are the first ever things discovered to impact longevity, the tools that we had prior to 1950 did not allow us to do genetics on the molecular level, they did not allow us to do any of the things that we now look at for longevity, the one thing, Alexis Carrel, in 1912, gets the Nobel Prize, for sewing blood vessels together. One of the things that is tried in the early half of the 20th century, because that’s the only thing that we had the tools to do, it’s like, literally you’re sewing blood vessels together, between a young and old mouse. That does appear to have positive impact. There are three or four Nature and Science papers that have come out recently showing, there’s some positive impact on the function of the brain, some positive impact on the function of the heart. Some on muscle, we do see positive impacts. I haven’t seen, to date, a really good longevity study. We see a lot of evidence of age related phenotypes getting better, but I personally have not seen a study that really makes me super excited about the number of actual years.

Laura Deming [00:59:52] – Lots of stuff indicated that might be the case, if done correctly, but, I actually haven’t seen a study done, yet. There’s been some studies, published in the mid 1900’s about parabiosis. I think that I might have cited, that kind of indicate and extension, but they’re not really replicated properly to really believe that. So, I think there’s probably some impact to life span, like, I don’t think we have it well characterized, yet.

Craig Cannon [01:00:14] – Okay, so true. Not a hoax, but…

Laura Deming [01:00:17] – Not a hoax! But, I think people really over focus on that, because it’s such an easy story to tell though, right? Like, “Oh vampires!”

Craig Cannon [01:00:24] – Yeah, vampires. I get it!

Laura Deming [01:00:27] – And you’re like, “No, no, no, there are like 60 different things that make… live longer,” and you have to look at, but you know, people don’t want to hear about daft tunes and receptors. They want to’ hear about vampires.

Craig Cannon [01:00:35] – Yeah, I mean, it’s just kind of like what I was saying before about tech being seen as like, black and white, like. Sort of like everything, people just want the pill. Oh, actually, I wanted to talk about Rapamycin.

Laura Deming [01:00:44] – Ah, right.

Craig Cannon [01:00:46] – My friend Nicola wrote a New Yorker article about it.

Laura Deming [01:00:50] – Oh, awesome.

Craig Cannon [01:00:51] – And, I’m like, I’m slightly terrified.

Laura Deming [01:00:54] – Right!

Craig Cannon [01:00:57] – Can you just break it down?

Laura Deming [01:00:58] – Rapamycin is this really, really interesting drug discovered on Rapa Nui, the isle in the as many drugs were, and, what it does is, many things. But one thing that’s been focused on is it’s impact on mTOR, which is a protein that’s part of two different complexes of proteins, and the problem for Rapamycin is to have a lot of side effects, right? It was originally developed as maybe and immune suppressant, in one use, and so, do you really want to be taking that continuously? Probably not. There are a lot of doctors, if you as a subset of the people who specialize in crazy things that might actually work in longevity, few of them will say pulsed Rapamycin. Taking Rapamycin in huge doses, but then, on a schedule, not continuously, is a good thing. We don’t see that being disproven or implausible, just kind of a risky endeavor on some level. One thing I would say, there are several companies trying to develop much safer versions, that do the same thing. Have the positive benefit. Don’t have all the other negative effects. I personally, would just kind of wait until those get farther along. But, Rapamycin is kind of report, the other fascinating thing is that, I don’t think we have a great feeling for what the max is on the life span that’s possible with Rapamycin. The question is, if you dose it up, what’s the maximum dose, and at what point do you start to get decreasing returns on longevity? And it’s not clear that we’ve actually hit that barrier, quite well.

Laura Deming [01:02:24] – That’s the other fascinating sort of thing.

Craig Cannon [01:02:25] – Interesting. Have you heard people taking testosterone?

Laura Deming [01:02:29] – Oh, yes.

Craig Cannon [01:02:30] – Kind of like, that is debated, over like, maybe it increases health span, but it actually might shorten life span.

Laura Deming [01:02:34] – No, because there’s a lot of people like, we’re in a low T society. There’s also a lot of people taking growth hormone for longevity. When I first saw that on the front of an air plane magazine, I was furious because like, in worms, if you knock out the analog of growth hormone receptor, they live longer. Dwarf mice are the long lived mice, and within a species, not between species, within a species, being smaller’s actually correlated with longevity. But I think, there is, one thing with taking growth hormone. Maybe taking growth hormone makes an 80 year old feel a lot better. It’s kind of like a health span optimization. Back to that, do you feel better, like, that results in a long life span. But I don’t think that’s a great thing to do obviously, for actual life span, in general.

Craig Cannon [01:03:16] – Because to clarify, it can increase or encourage cancer cell growth?

Laura Deming [01:03:22] – There’s possibly some minor thing there, but I think, for the most part, there’s a not fully defined, complex healing pathway that seems to be quite related to longevity that was first discovered in worms, and then also occurs in humans. There’s a subset of dwarves, for example, who-appear, compared to their relatives, suffer much less cancer, and metabolic disease. That correlates to what you’d expect from mice. If you mutate mice, to be dwarves, they live about 60% longer than normal. 60%! Pretty non trivial!

Craig Cannon [01:03:54] – Pretty solid!

Laura Deming [01:03:55] – Right!

Craig Cannon [01:03:56] – How much shorter would you be, if you could live 60% longer?

Laura Deming [01:03:58] – How much shorter? I’m not quanta, I don’t know, not 10%, obviously, but maybe between 50 and 70 or 80. I don’t know actually, for sure, for those mice, how much more they were quantitatively. The interesting thing is, you can actually possibly decorrelate the being smaller, with the effect. So it’s not just like a size it’s like a thing, as well.

Craig Cannon [01:04:20] – Would you make that trade? If you were one foot tall?

Laura Deming [01:04:22] – The trade is positive! The idea is like you can decouple being small with longevity benefits.

Craig Cannon [01:04:27] – Oh, I know, but I’m asking you, would you rather?

Laura Deming [01:04:28] – Oh, but would I be willing to make that trade off? Yeah, probably.

Craig Cannon [01:04:32] – Probably? That’s awesome. Aubrey de Grey, another famous longevity person, someone asked about them, so, Chris asks, “He’s mentioned several times about replacing organs with new organic ones, before they fail. Is that a reasonable idea, or would they more likely be replaced with synthetic ones?”

Laura Deming [01:04:52] – Oh, interesting. This is an area where we’re still building our, it’s maybe too late to be seven years in, and still be thesis building, but I think, there are so many things that have to go right, for that to become the obvious thing to do. In some ways, it’s like the oldest version of aging, right? Back to our friend Alexis Carrel, and his Nobel prize for…Hhe is doing the first ever, kind of like, sewing up the organs, and maybe if you read his paper, “Let’s just grab this dog kidney, and we’ll take this one, from this other dog, and like, plug it in.” Wow, can that the early 1800’s. In a sense, what Aubrey’s proposing is the oldest, most worked on idea. But then, I think we also haven’t seen that done well, on the rejuvenation front, a lot recently. We’re still falling short, there are some things where if you get an organ from somebody who’s had cancer, for example, there’s a small risk 10 years later you might also incur some kind negative event. There’s things that we’re still understanding how to weigh those risks.

Laura Deming [01:05:54] – I think it’s fascinating, it’s a surprising fact that it sounds the most futuristic, but is actually the most old method of considering, working in this space.

Craig Cannon [01:06:02] – Right. Well, you’re just like, “Take the part out, put in another, good to go.”

Laura Deming [01:06:06] – Right.

Craig Cannon [01:06:07] – All right. I have a very important question. Micah has said you did a cookie diet? Is that true?

Laura Deming [01:06:15] – Yes, yeah!

Craig Cannon [01:06:17] – How did that go?

Laura Deming [01:06:18] – I think it was pretty informative in that I wouldn’t recommend that anybody to go eat just cookies, but…

Craig Cannon [01:06:22] – Were were these like fancy health food cookies?

Laura Deming [01:06:25] – No, no. So, the reason I did it was that my friend had claimed that he had only eaten whipped cream, and bacon, for a month, and that this was possible,

Craig Cannon [01:06:35] – Of course it’s possible!

Laura Deming [01:06:38] – But then he was like, “But I actually feel pretty good, too.” I thought that it was total B.S., and that he, and he’s a very smart, and conscientious person. I was like, “Well, either he’s very different than I thought he was, or, that’s possible to do.” And so, I wanted to test it, and so I tried that, and I was like, “Well, you actually kind of can and you kind of feel fine.” I was just curious, if you took any random thing, like any random food object, and just ate that for a month, what would happen? And the cookie diet worked very well. But, for the long term, it seemed like not a good idea, so switching off of that to a lower sugar diet’s probably a good idea.

Craig Cannon [01:07:11] – Were you doing blood tests or was it all by feel?

Laura Deming [01:07:14] – No, no, I should have done blood tests.

Craig Cannon [01:07:16] – That’s funny. Yeah, there was this well known, long distance hiker, named Andrew Skurka, who wrote a bunch of blogs and stuff, and he’s pretty well known for having kind of extreme, he just has a diet that can take anything, it seems like. I think for a while, it was just like Snickers, and Pringles. Something like that.

Laura Deming [01:07:36] – That sounds great.

Craig Cannon [01:07:38] – I guess if you have enough toothpaste on the Pacific Crest Trail, you’re fine.

Laura Deming [01:07:43] – You have to kind of wonder, though, how much worse that would be than… One good example is a lot of eating meat. Maybe the worst part of meat if your animal is stressed. How a lot of the incorrect type of hormone directly before being killed. But actually, a more important thing, whether you’re eating meat or not. What are the minor things that we don’t think about? The actions that aren’t explicit. What those are?

Craig Cannon [01:08:04] – Yeah, hard to say.

Laura Deming [01:08:06] – Hard to say.

Craig Cannon [01:08:07] – Cool. All right. My last question is, are you seriously not doing anything weird? There’s no pills, there’s no weird food, there’s no crazy fasting?

Laura Deming [01:08:15] – Apart from trying the cookie diet, one thing that I was trying to do for a while, I was trying to quantitatively understand because, we’re just black boxes and you intake some number of calories. I’m like, “You should be able to calculate where they all go. How many are necessary to eat, each day.” From first principles figure out, what an awful diet would be. I tried to do that for muscle. I was like, “How many proteins should we eat 30 minutes after working out?” The first problem was, it’s really hard, why 30 minutes after working out is the correct amount of time? I have no idea, because our cells are expanding during that period of time, but, it’s hard to figure out. Also just got, really down in the weeds of how many amino acids have you required to replace certain things, and I think I came out of that very convinced a lot of the things people talk about, at a high level, wrong. Provably, theoretically, at a lower level, and that, I just didn’t have the time to really think about doing that for so, I think at this point, until I have maybe a full year to go back and maybe understand that whole area better, the obvious things, because history’s probably a good teacher for baseline health.

Craig Cannon [01:09:21] – Nice. All right. If someone wants to learn more about you where should they go?

Laura Deming [01:09:25] – Yes! We run Longevity Fund and I’m just laura at longevity dot vc and anyone can reach out. We love to talk to you.

Craig Cannon [01:09:32] – Cool, thanks for coming in.

Laura Deming [01:09:34] – Awesome! Thank you for having me!

Craig Cannon [01:09:36] – All right, thanks for listening. As always, you can find the transcript and video at blog.ycombinator.com. If you have a second, it would be awesome to give us a rating and a review wherever you find your podcasts. See you next time.