Do We Have to Die? with Venki Ramakrishnan

29:11They're imagining themselves in another universe in a way being reincarnated and living forever. It's like, no, that's a different person. No, that's just a different person in a different timeline. And by the way, these transhumanists, people who think that they're going to dump their brain into a computer and then maintain their consciousness, a simple question to ask is, what if you make two copies of it? Which one's the real you? And they immediately have a paradox. Absolutely. The copies that you make will be of you of that moment, but you've, in your timeline, are still proceeding. Yeah.

29:42They would be stuck. You still get to go to the beach and have friends, and your brain in a jar does not. Right. Oh, gosh. Or your brain in the silicon chip. It's you from whenever it was you created it. So I heard long ago, and I checked it out, and I think it's true, that all mammals live for about the same number of heartbeats except for humans who live two or three times that. Except if you go back far enough in time when we were just living in caves, we were right with all the rest of the mammals. So first, is that true? Second, there are animals, not mammals, that live much longer than we do.

30:20I'm thinking of the Galapagos tortoise, for example. So do you guys study other animals to get insight? So there is a whole field devoted to looking at lifespan of different species. And you are right that, at least among mammals, Jeffrey West, who's written a book called Scale, shows that the number of heartbeats is roughly the same. That has to do with the fact that smaller animals have a higher metabolic rate. They have a faster metabolism. And they almost need to because their surface-to-volume ratio is larger. They dissipate heat more. We did a whole explainer on surface-to-volume ratios.

30:57And so they need to maintain a higher metabolic rate. That's one of the reasons. Well, that's only one of the reasons why they have higher heart rate. That's not a reason why they should die sooner. Ah, the why you should die sooner has an evolutionary explanation. And that is evolution doesn't care how long you live. It only cares about fitness. Fitness in the biological sense is the likelihood that you're going to be able to successfully pass on your genes. And people always misinterpret that as being physically fit or stronger or whatever. Survival of the fittest as in, I'm in great shape. Yeah, Jarwin should have found a different word for that.

31:41So evolution cares about fitness. Now, at the same time, for most of our history, and certainly the history of all other species, resources are limiting. And so you have to select, do you put more of your resources into maintenance and repair of the individual animal or do you put it into growth and reproduction? There's always a balance if you have limited energy. So in the case of a mouse, which lives about two years in the wild, there's no sense in having a mouse live for 40 years because long before that, It's going to be eaten. Eaten, yep. Exactly. You beat me to it. Or it'll die of starvation or drought or something.

32:28And so in the case of a mouse, evolution has favored selection of a species that grows very quickly and reproduces prolifically. That's a mouse. If you get to a large animal like a bowhead whale, let's take an even bigger than an elephant, they can live for 200-300 years and they have a relatively slow metabolism and even slower metabolism is not a mammal but it's still a vertebrate called a Greenland shark 700 years a vertebrate living for 700 years very slow metabolism how do you know that? we didn't even have marine biology 700 years ago they can do things like carbon dating they cut one open it was with 700 rings inside.

33:18I mean, you've got... Okay, I'm just weird. No, no, no, no. So you've got the mayfly lives a day. Mayfly lives a day, exactly. And in between that, you've gone from there to a Greenland shark. And your Galapagos... And there are actually other animals that are thought not to even age biologically. What's the immortal jellyfish? Like the hydra and the immortal jellyfish. These things have... Wait, there's an actual animal called the hydra? Yes, that's right. Awesome. Not just in... Not just in GI Joe? No, in... Oh, no, Marvel. No, no, no. Oh, in Greek legend. Oh, you mean the real hydrogens. Yes!

33:49This is a freshwater small animal. And they're full of stem cells, so they're constantly regenerating themselves. But if you followed an individual, it would also age only very slowly. It's just in the wild, it dies for other reasons before actually aging. So there's a whole range. So humans might be the only species that dies of natural causes in the world. I mean, if you want to think about it that way. It's possibly, you know. We're apex predator. Yeah. So. Yeah, I think that may be true. In fact, there's a book written by Stephen Ostad called Methuselah Zoo, where he talks about all these animals.

34:32And he talks about it. Methuselah Zoo. Love it. And it's a great book. So that reminds me, because Methuselah is the oldest person in the Bible. Right. in the Old Testament Bible. The oldest star we know of in our galaxy is called Methuselah. It's called Methuselah. Yeah, right. So Methuselah had a lot of influence. Yeah, and that star too is lying about its age. Who knew that? Anyway, in this book, he points out. Methuselah Zoo. In Methuselah Zoo, he points out how all these species have such different lifespans. and it's because of this evolutionary selection, but it's actually worse than that.

35:15The fact is evolution will select for things that help you early in life, even if they cause a problem later in life. So many of the things that cause aging are related to growth, for example, or to cancer prevention, prevention of, or senescent cell creation. These things all help us early in life and they're a problem later in life. But evolution doesn't care what happens to you when late in life. When not making babies. Exactly. Because that's the whole deal. So what helps us survive in infancy and then go on to reproduction is the key component of our decline and demise. Not always. Not everything.

35:54But there are things that happen to us early in life that are selected for early in life that cause aging. So the real deal is just keep having babies your entire life and then you'll never age. However, you will eventually kill yourself because of these kids. So we're an outlier. We're an outlier. We live about twice as long as we would based on our size. But only post-caveman life, right? Yeah, 40 ,000 years. Exactly. So only, I mean, half of everyone died by 30. And so we're not 2x other mammals at our size. Yeah. And one last thing is there's a group of animals, mammals, the bats. They live much longer.

36:40They're about the same size as a mouse in terms of mass. If you're a mouse. They live about 10 or 20 times as long as a mouse. And the reason is they can fly around. So that means two things. They can escape predators more easily. Right. And they can also forage over a much wider area for food. and when they roost, they roost in the ceilings of caves so they're not as accessible to predators. They've been designed to survive longer. And so there is worth it for evolution to make them live longer because they'll still keep producing more babies. So you've got to be Grandpa Munster is basically the deal.

37:21Grandpa from the Munsters. Grandpa from the Munsters if you want to live long. Sleep hanging upside down away from predators. So if we're looking at aging, we all do it, can't help it, more or less, what have been the attempts to reverse the aging? I'm not talking potions and lotions here. So let's go through the laundry list. The sort of young blood transfusion. How successful has that been? It's not incredibly successful, but the science underlying it is solid. If you connect an old rat with a young rat, By that I mean you connect them so that their blood systems are joined. Sharing the same circulation system.

38:03Exactly. Then it turns out that the old animal benefits from the blood of the young animal. But even more so, the young animal suffers from the blood of the old animal. Wow. And so this means there are factors in blood that change as we age. Such a thing as old blood. Exactly, or young blood. I call it vampire blood. So that's the science. And the research is now about finding out what these factors are, what they do. And once you know that, you might be able to figure out whether you can use them to our benefit. But people have not waited for that. What's happened is the very first time these people from Stanford, Rando and others, published this, they got creepy phone calls from rich people asking where they could get blood.

38:55And companies started sprouting up, getting blood from young donors and extracting the plasma and setting them up at$8 ,000 a pint or something to rich old people. And one of them, the FDA, wanted to shut it down and then they sprouted up under a different name. The whole thing was like the Wild West. But there's real science under it, and that's an ongoing area. Okay, stem cells we've kind of addressed as to how you can, through the Yamanaka factors, dial up, dial down. And that's, I would consider that... Yamanaka. What is the Yamanaka factor? The Oscar winning, where he sort of... The Oscar winning?

39:38Yes, Oscar winning. He was a bloody good actor. He was an unbelievably good actor. Nobel Prize winner. Okay, that guy. Right, that guy. Thank you. Okay. The Nobel Prize winner. Get your prizes straight here. Okay. The calorific restriction or caloric restriction. Yeah, so... Basically, it's fasting. It is. It is. So, lots of experiments, starting in mice, but now also in flies, worms, even in single-celled animals like yeast. If you reduce the amount of calories, it turns out that you can, the animals live longer, but more importantly, older animals start resembling younger animals in terms of their physiology and their biomarkers.

40:21And so the question is, can you mimic caloric restriction? And it turns out that there are many important biochemical pathways that are affected by caloric restriction. One of them is the IGF-1 insulin growth hormone factor. Just to be clear what you're saying, you wouldn't have to imitate calorie reduction. you could just consume fewer calories. So what you're trying to do is we can still eat our cheeseburgers and the blueberry pie dessert, and then you hijack what would be the starvation mechanism biochemically. Exactly. That's intermittent fasting. Yeah. But I don't have to fast. Is this the GOP?

41:07Oh, yeah, the whole point is not to fast, just to restrict, yeah. No, no, no, no. Did you get what I just said? No. What he's saying, That's why I paused on it. Saying, have your cake and eat it. Say, have your cake and eat it too. Yes. Explain your point again, because I missed it. Okay, so the point is, what he said, he just slipped it in. Right. But I caught him. Okay. He's saying, fasting will prolong your life. Absolutely. So can we find a way to mimic the biochemistry of that in your body? We can. And the word mimic in that sentence means still eat the cheeseburger. Right. But do what the fasting would have done to your biochemistry.

41:45I see what, yes. Have your cake and eat your cake. But you're doing it artificially is what you're saying. In my book, I call it eating your blueberry pie and ice cream and getting the benefits. Nice. And still getting the benefits. Wait, so have we done this? No. Well, there are some drugs. He's working on it. Okay. No, no, I'm not working on it. He's like, I'm out this game. I should say. He was like, did you see? Yeah, the way he said it. He just went like this. No, no, no, not me. Hey, hey, they keep trying to keep me working. I'm telling you right now, I'm out. But if you do know how to do it, tell Chuck, because he'll set up a company.

42:18No, there are lots of companies. That's a problem. So anyway, one of the drugs that does this is called rapamycin. It's the darling of the anti-aging research community. This is the Easter Island find, isn't it? Easter Island. Yes. Easter Island is where it's coming. Yeah, rapamycin. Okay, let's do it. So rapamycin was found in the soil of Easter Island, from bacteria in the soil of Easter Island that produced this compound, which turns out to be an antifungal compound. And then they found out that it may have some properties against cancer. And then eventually they found out that it actually is an immunosuppressor.

42:59And that's what made it get FDA approval as an immunosuppressive drug. Then, much later, it was found in a completely different place. It was found that it shuts down a major pathway in the cell. And that pathway is related to the, it's a pathway that senses nutrients. So it's related to caloric restriction. People then said, okay, let's see what happens if you give rapamycin to mice and so on. And mice lived a bit longer or seemed a bit healthier. However, rapamycin is an immunosuppressive drug. So it's going to make you more prone to infections. Like steroids. And it has other side effects as well.

43:43Okay. So the question they have is, can you adjust the dosage so you get the benefits against aging without the problems of immunosuppression and so on? And that's still, jury's still out on that. Yeah. Okay, now there's also relativity. where you can slow down time for yourself. Oh, well, that's going into space, though. Yeah, well, right. That's one way to defeat aging, right? However, you are still aging. Right. In your own body, one second per second. Right. The difference is all your friends are aging faster than you. Much faster. Right, right. So you're not going to live older than you would have as an organism.

44:22Right. You'll just live longer than everybody else. Exactly. And then when you return, all your friends would have been dead. They'd be dead. The Kelly twins, they did the experiment. Oh, yes, yes. We had one of them on this program. Yes. Scott Kelly, astronaut who went up. That's right. And his brother stayed here. His brother stayed here. They're identical twins. And you can calculate how much younger one would have been, like a fraction of a second. That's what he gained? He gained half a second, huh? Does it show? So basically, yeah. Does it show? Excellent. I don't remember the fraction, but they were not going so fast that the speed of light, time dilation.

44:58That is the definition of sibling rivalry. Yeah. The most expensive anti-aging regimen ever.

45:24So, as you surely know, in physics, we speak of this thing called entropy, where left to itself, a system will always degrade to lowest energy, highest disorder. The key is left to itself. Yes, yes. So we can create any manner of complexity on Earth because we're not a closed system. We're open to the sun. So the sun is gaining entropy by helping us out. Eventually it's going to die and nothing's going to help it. Right. So do you guys in molecular biology think of entropy? There's no question that entropic forces exist. But, of course, living systems all use external energy to keep it alive. And part of the energy is used to do this maintenance and repair of the damage.

46:21But it's not perfect. And so eventually, even if you keep repairing DNA damage, repairing cells, getting rid of defective cells, all of that stuff which takes energy, it's not perfect. And eventually the system gradually decays. But it means it decays at different rates for different species. Interesting. Or different parts, different systems even within your own body. Oh, that's something that's very interesting. So if people were to analyze your different organs, that find they all had different ages. Yes. To say someone's biological age is a number. Different ages mean different time distance from its birth to its death.

47:03Correct. Right, because obviously it's all physically the same age. Physically, chronologically it's the same age. Yes, but physiologically they're different ages. But it doesn't make a difference because if I got an old heart and a young pancreas, I'm still going to die. With a heart issue. With a heart issue. So that was always what I suspected, that people who live very long, all of their organs somehow are aging at the same rate physiologically. Well, I don't know if that's true, but maybe they're still aging differently. But the lead organ, the organ that's aging fastest, is still slower than other people.

47:41Right. Right. If they die, it's not going to be from that. So given what you just said, I didn't put two and two together here until just now in the second law of thermodynamics. one of its stipulations is if you have sort of usable energy over here and you convert it into another kind of energy over here, there's always energy losses. Always. That's why you cannot make a perpetual motion machine. Right. And so the body is all about converting energy of one kind into another. You have chemical energy in food and you turn it into... Yeah, exactly. Remind us about that. We all learned it in biology class.

48:21The ATP cycle, is that right? ATP is adenosine triphosphate. It's a molecule with high energy bonds. So you can think of it as a universal currency, just like in our world, electricity is a universal currency. So you use everything converted to electricity, then you can use that for everything. And so the body uses it, so you can think of it as a kind of storable form of energy that it can use. Right, but it's taking energy from one thing and converting it to another thing. Typically in our case, we're getting it from carbohydrates. Yes. And by burning carbohydrates - So it's chemical energy. It's chemical energy.

49:00Yeah. So that energy is used to make ATP. Got it. And anything else we make in our body to maintain our body temperature because we're warm-blooded, to move. So it goes to thermal energy, kinetic energy, and the like. And most of those things involve ATP. And electrical energy. Right, for your brain and your heart and signaling and all that. So I'm just saying, every time you convert from one form of energy to another, you're getting less energy than you started with. So there is a decay in there eventually. Interesting, yeah. So you describe this sort of implicit value of death to a species because it doesn't need you after a certain point of your fertility.

49:44We're beyond that now, and we're what we call civilized. And so there are people who want to do anything they can. To stay alive for as long as they can. To stay alive for as long as they can. And you're in that business scientifically. What is the ethics? I should say my own lab has never worked on aging. I went from zero to expert in one book. Oh, okay. Okay. My lab works on protein synthesis, which is a central component of aging. I don't actually do aging research myself. Okay, but surely you've thought about the ethics of it. Yeah. Why wouldn't you have? Oh, definitely, yeah. Yes, yes. And I also have no skin in the game, so that's...

50:25Okay. That means we can get a very truly objective... Other than beautifully soft skin. Right. I missed that one. Yeah, Chuck, I don't want to be ahead of you on any of this. That was a good callback. I like it. Chemical laws, biological laws, any in the way to stop us going from where we are now to potential immortality? Right. So there are two issues. One is, is aging programmed? I mean, are we all programmed to die? Yes. No, because evolution doesn't care about... It doesn't care about us dying. So there are genes that affect aging, but those genes don't exist in order to make us age. They were selected for some other reason, but they happen to cause us to age.

51:05So now that we understand some of the biology of aging, you ask, can we extend that? Yes. And there are no physical or chemical laws that say that we have to die at 120. I mean, 120 is about the record for humans. Very few reach that. And by the way, whenever you see a 120-year-old, they're like, I am ready to go. Oh, I'm not sure. It's like, don't take me to Disney World. Take me now. Not all of them, but yeah. No, there's a woman, Jean Calment, who's the record holder at 122. Oh, she was the smoker and drinker. She used to smoke and drink into her hundreds. And reporters, after a while, used to gather at our house every birthday.

51:52And one of the reporters said, well, see you next year, I hope. And you know what she said? What? She said, sure, why not? You look pretty good to me. It was pretty good for her. But there's no physical or chemical law that says, you know, at 120, you got to go. There are species, as I said, that live 700 years, vertebrates. Of course, the question is, can we change our biology to make us live much longer and still keep us humans? You don't want to be a very slow metabolic animal like a Greenland shark. You still want to be human and you want to live much longer. Now, there are people, I would say, at the one end of the anti-aging research community, including perhaps somebody you've had on your show, who think that it is possible.

52:47You can just keep extending life and that'll buy you enough time to do more research and you'll extend more life. And eventually, there's a generation that would reach the escape velocity. Exactly. Where the prolonging of your life is one year per year, and then you live forever. Yeah. Now, I'm highly skeptical, as are most scientists in this field, because aging is a multifactorial process. And to be able to do this in a way that's safe, that's efficacious, that actually works, I think is going to be very, very hard. Certainly not impossible. The Google software that uses AI for folding proteins, which won a Nobel Prize, if memory serves, won't that solve all your protein folding problems?

53:33No, this is different from, I think AI will have a big influence on biology. And maybe one day it will help with things like aging. One day, 18 months from now. Some time in the distant future of AI. What time is it? Okay. Let's say I'm highly skeptical, but there is no physical law. But I'd say there's also no physical or chemical law that says you can't colonize other galaxies or even Mars. And so, you know, whatever Elon may say, it's not going to happen tomorrow. So I think... And I think we should get down here kind of worked out first. I'm sorry, but... Yeah, why don't we make this place habitable?

54:20All right, so what happens the day we as chiefs escape velocity? What happens to civilization? I think before that, a number of things will happen. For example, more people may live to be 100 or well into their 90s or early 100s. That itself will cause a huge shift in society. For example, fertility rates everywhere are dropping. And so what you're going to have is a society. It's an aging of the population. Yeah, society where there's very little turnover. Same people are living longer and longer, very, very slow turnover. To me, that means a less dynamic, less vibrant society. If you look at the history of science or any fields, even literature, people have done their most creative work when they're young.

55:10And it's not just about physiological age. When you're young, you're looking at things fresh. You're not as opinionated. You're not dogmatic. And that allows you to think out of the box. You have to convince the old people that they're less useful to society. How do you do that? Well, one of the reasons I'm retiring is because I decided four or five years ago to close down my lab. It's going to happen late this year. It's partly because I do believe that when you've had your time, you should step aside and let younger people carry on. Carry on. When Einstein was given the option to be operated on, basically on his deathbed, he said, no, my work is done.

55:53My work is done. Yeah, I would have said, what kind of doctors are you? Save me. Thank you. What you were talking about is inverting the population pyramid. So it goes from a small peak of aging population to a rather large one and less young people. We are basically diving down a drain here. It would be more stable the whole time. More stable. Yes. Stable thing would be good, but if the turnover is very slow and people just live for very long, I mean, as people get older, they accumulate power, they accumulate wealth, they accumulate influence. And, of course, the three go together. And that then means that it's harder for younger people to gain entrance, to make it, and so on.

56:40To make that work. And that's a real problem. Sociocultural fact, yes. And that's a real problem. We're seeing that right now in a certain party in America where they're like, yo, everybody who is in charge is 80 years old. Get out of the way because we have a different way to do things and we want to get to it. Interesting. And so I think societies would be more stagnant and less dynamic and less creative. People will always throw exceptions at me. Oh, so-and-so was so brilliant late in life. But those are exceptions. You know, that's not what you plan a society around. But here's the problem.

57:18If somebody gave you a pill and said, this is going to give you 10 extra years of healthy life. Nobody wants to be sick for 10 years. 10 years of extra healthy life. Would you take it? I know I would. Yes. Okay? Almost all of us would. And this is the conflict between what we as individuals want and what's good for society. Right. Because at the end of those 10 years, if you're given the option again, you'll probably say yes again. Exactly. Right. Absolutely. Especially if it's healthy life. So that thought experiment takes the larger question down to its individual parts, and you realize people really do want to live forever.

57:53They do. Well, because, yeah. They do. Because this is, as you say, the only life we know. It's our existence. We fear the loss of existence. And that's the problem. You know, there's, I mean, I'm about to get philosophical. The great thing about death is that when you look at it full on and embrace it for what it is, it allows you to wake up and treat each day as something special because you know this thing is going to be over. If you take that away, you know, I don't give a damn. People have said that, that having a finite life gives you the drive, the incentive to accomplish things. Otherwise, there's always tomorrow.

58:36There's always tomorrow. Okay. So that is true. But at the same time, there's an old joke. Who would want to live to be 100? And the answer is always someone who's 99. So you may be philosophical about death in the abstract, but you don't want to die next year. Well, no, you're absolutely right. I don't want to die, period, because my life is pretty damn good. And we're not talking about people who are so mortally injured or ill that death feels like an escape. We're talking about someone who's fully... Who's vibrant. Vibrant, yes. There's also one aspect of aging research. If you ask most of them, they'll say, except for some of these outliers, they'll say, oh, we're not about extending lifespan.

59:20We're about increasing health in your life. And the idea is that you stay healthy all your life and then suddenly, you know, crash and die. And there's a poem called The One Horse Opened Shea. I just learned about that poem. It's the horse that... The carriage. was perfectly designed so that it wore out. All its parts wore out equally. Exactly at the same time. And one minute the farmer was riding along, the next minute he was on the ground surrounded by a bunch of debris because his whole carriage collapsed. Now that's what people are asking when you say, we're going to compress the period of morbidity in old age and we're just going to suddenly decline and die.

1:00:05Nobody's shown that that can actually happen. Apple is working on it, believe me. Nobody's shown that. So if they increase our health span, it's equally possible that they may extend - I like that, health span. Good phrase. Not lifespan, health span. Yeah, but if they do that, if they keep us healthy in old age, it's equally possible that they extend our lives too. And that eventually we still have that slow decline. Oh, you still have the - You just reach a point where now I'm 108 and it's all falling apart, but I'm not going to die tomorrow. is still going to be a slow, archless death five years from now.

1:00:40Yeah, yeah, yeah. Of course, if we live forever, we need to find another planet because the population will continue to rise and we will outstrip the resources of Earth and possibly Mars, Venus, and any place else we search for. That isn't quite true. What? Okay, if birth rate went to zero, then it's not a problem. Exactly. But who wants that? Well, first of all, you're not going to have complete immortality. mortality, you're going to have extended lifespan. So the birth rate simply has to fall in accordance with how much you've increased your lifespan. There you go. And in fact, if you look at Korea, South Korea, or Japan, it's happening.

1:01:18People are living longer, and yet the population is going down. It's going down. So, Venki, this conversation has been delightful and illuminating and enlightening. I can't wait to die. You're going to have to. And after we're done with this episode, he's going to whisper to us that he's 150.

1:01:41On this topic of why we die, we covered so many nuances of it. I'm left with very little to offer as a cosmic perspective. What I will say is that, speaking for myself, I, at this stage in my life, value the knowledge that I will die. because that gives meaning to every day that I'm alive, knowing that there's one fewer days left in my future to love, to have new ideas, to make discoveries, to embrace all that it is to be alive in this world. If you look at it mathematically, if the knowledge of death is what brings meaning to being alive, then to live forever is to live a life with no meaning at all.

1:02:46If you can just put off to tomorrow what you could have done today. Will I think this on my deathbed? If I'm offered a pill that can make me live another 10 years, when I'm on my deathbed. Would I take that pill? I don't know. It's kind of easy to talk about death when I'm pretty sure I'm not near it in this moment. But I will say, I reserve the right to revisit the option of living a little longer when I'm on my deathbed. But for now, knowing I'm going to die is what's keeping me going. And that is a cosmic perspective. Chuck, good to have you, man. Always a pleasure. Gary. Pleasure, my friend.

1:03:29All there. This has been StarTalk Special Edition. Topic, why we die. Until next time, Neil deGrasse Tyson, your personal astrophysicist. Keep looking up.