Make People Better podcast
episode 2: Immortality https://www.buzzsprout.com/2142608/12377476-immortality
transcriber's note: Any errors are my own; this is not a machine transcription and it's just me typing and I don't review it. Submit any edits to the wiki.
As far back in recorded history, from ancient cave paintings to the pyramids, humans have quested for immortality. It's the ultimate prize for a species that can imagine the future and their own eventual death. In recent years, science has transformed that quest into a technological one: advances in gene therapy for the first time have unlocked very real research pathways. We have entered an era where aging is thought of more as a disease that can be stopped rather than an inevitable feature of life.
George Church: You think about how much revolution has happened in the last 10 years in terms of reading and writing DNA. Imagine though what we could achieve in the next 10 years and the next 40 years.
Noah Davidson?: We're at the step of translating it from mice to dogs. We have done several tests in dogs now. The next step after that would be into humans potentially.
Max More: The whole idea is that you come back as a young person. You look in the mirror and go "damn, I look fine".
Andrew Hessel: I wish I had a thousand more years to see how this plays out.
((intro))
Cody Sheehy: Many scientists familiar with this research believe that it is likely that gene therapies have the potential to extend our healthspan, which is the span of time during which we are healthy, to at least 120 years. Where the technology goes from there is less clear. It's plausible that all the mechanisms related to aging and decay will be solved.
Samira Kiani: This episode will include our conversations with Andrew Hessel, a microbiologist and futurist. Max More, a former president of a cryogenic facility called Alcor. The next stop will be to meet with George Church the legendary genomics pioneer who has started Rejuvenate Bio with Noah Davidson. When people see the possibility of radically increasing the lifespan of their beloved pets, they will then become more comfortable trying the same therapy on themselves.
Concept of immortality
Cody: For me, the concept of immortality is a little tricky. One way to think about it at least as I do is that my body and my consciousness and everything that makes me "me" is aging and someday I'm going to die. If I could just prevent that process forever, then that's immortality. But from the point of view of an evolutionary biologist, there's part of us that is already immortal and that's the DNA that is safely held inside of me. It has been evolving and passing from generation to generation through each of my ancestors through time and now it's inside of me. I already have a son. It's going to continue safely on into the future through him and to his children and his children's children. From the point of view of DNA, it's already immortal and my human body is kind of a temporary shell that is housing my DNA just for a little period of time.
Samira: I like the angle of immortality of human DNA from the evolutionary perspective. If you talk about removing death, I always feared death. I never wanted to think about it as a child. I wanted to remove death. I still love that idea. Another part of me has started to look at life differently and that we have a purpose on this world and we're in a path of spiritual growth and death is part of that process. But if you look at it from the angle of increasing healthspan? I would jump at it. Let me give you my personal reason- I'm 41 and I wish my fertility age could be extended somehow so that I could have my own biological child. I want that. But the idea of removing death altogether? I don't think I want that. I don't think life or that the purpose of it would exist as we think of it today without life.
Cody: What if the supreme leader of North Korea never died and ruled over North Korea forever?
Samira: That would be horrible.
Cody: It's interesting to look back in history a little bit and see wealthy powerful people who become obsessed with perpetuating themselves forever. I think they are caught up in that early phase of maturity that you described. Like the pyramids, these monuments to the pharaohs. Do you know much about the pyramids? What was their purpose?
Samira: The pyramids were some of the earliest concepts of immortality going back to 3,000 BC. They were one of the first civilizations to believe in life after death and that the soul meets another body and starts a new eternal life. They wanted to be comfortable. Pharaohs filled tombs with important things they wanted to have in their eternal life.
Cody: When they had no way to stop aging and prevent death, their solution was to create a new life after death a sort of metaphysical after-life. When I look at the world's religions, this is a core component that they offer to everyone. There's another thing that I have noticed too. It's another way to claim immortality is to make your mark on history. I see powerful titans of business or empires and conquerers that are trying to reshape the world and name everything after themselves as an example of them trying to make a mark on history. It reminds me of the movie Gladiator which is one of my favorite movies. The opening scene where Russell Crow is giving a speech to all the soldiers before they go into battle and most of them are going to die.. let's listen to it. Hold the line. Stay with me. If you find yourself alone, fighting in green fields with the sun on your face, then do not be troubled. For you are in Alyseum and you are already dead. Brothers, what we do in life echoes in eternity.
Samira: You know, all of these points as I said are centered around metaphysical immortality. There's a long history of people actually seeking actual physical ways to stay alive forever.
Cody: There's a few examples of this. One is the fountain of youth which is a fountain where you drink this water and you get restored. Or King Author's knights searching for the Holy Grail and if you drink from it it would supposedly restore you to your youth and you will live forever in youth in happiness and it's an actual potion.
Samira: It's interesting that in the modern world a technology centered approach is how these ambitions are being expressed now. I thought our interview with Andrew Hessel captured these ideas very well.
Andrew Hessel
Andrew Hessel is a microbiologist and geneticist and an entrepreneur. He's also a prolific speaker and advocate of promoting the positive benefits of synthetic biology.
Samira: Andrew, how does a microbiologist think about life?
AH: The way I think about life is that it's information processing. The information processing in this case is done with molecules. It's an information processing entity- the cell takes in information from its environment, it processes it, it does calculations, it makes decisions, and yes it's controlled by a digital code the operating system or genome of the cell. The entire system is functioning as a molecular computer.
Samira: What is your perspective on death?
AH: Well, I think death makes life a little more meaningful. Anything that has an endpoint or a deadline I think is motivating. I don't worry about death too much. There's no reason for anything to truly die any more. One of the things I found really fascinating being a cell biologist is that we can take samples of a more complex organism like a few cells and put them in a freezer, pull them out later, a sample, and continue to grow them. Who knows what technologies we will have in 20, 50, or 1,000 years? There's no reason for our genetic programs to be lost to time any more.
Cody: So you're predicting that we will understand biology eventually that we could truly capture immortality and ever-lasting youth?
AH: When it comes to the biological process of development and aging, it's pretty scripted. The first- from the formation of the zygote, sperm and egg meeting, it runs a program. Just speaking for humans here. It runs a program that ultimately produces the development of a baby. I'm learning this because I have two small children. It's a program. it's scripted. They know about the milestones for development at 1 year, 2 years, 3 years. It's pretty much a program. Once you get to the first couple of decades, at 20 years, you basically have run the biological program but now you are running the social program the nurture part of human biology. Now you're trying to just have your life. You've learned how to walk, talk, eat, defecate, reproduce, copulate, and now you are starting to really move into the next stage of 20 years of growth which is really when we lbossom professionally, socially and as individuals. In the 3rd decade you get to enjoy it and enjoy your children going through the process too. In the last 2 years, you kind of just decline and die. Just trying to figure out how to slow or stop aging or reverse aging are all really new areas of biological research.
AH: I'm absolutely an optimist when it comes to these technologies. There are certainly risks and we will learn from them and course correct. I know from actuarial tables that I have until my mid 80s. That's not so long away. My risk tolerance for this type of manipulation and engineering actually grows over time. I would use more and more biotechnologies as I get older to sustain myself without-- and taking the risk personally because I know what the end game is.
AH: It's one of the most exciting times right now to be alive. All of the sudden we're not just at the mercy of our machinery. We get to open up the hood and tinker with it and think about where we might want to take it. I think that's just a staggering shift in human evolution. I hope it excites people more than it scares them because really a life just running the standard program where you get born and die we know what that's like. It's short. It's fleeting. I wish I had a thousand more years to see how this plays out.
Techno-optimism and transhumanism
Cody: One thing that I really like about Andrew is his optimism. I actually feel like all the people we talk with about immortality over many years now- they seem to have that trait in common.
Samira: Yes, I agree. Technology is viewed as completely beneficial in the long-run. This techno-optimism has inspired an entire movement of supporters and early adopters who are now called transhumanists. One of the original founders of the transhumanism movement is the British philosopher Max More. They aspire to augment human intelligence, physical ability, and lifespan, with an evergrowing mechanical and biological enhancements. The end goal is that humanity will eventually transition from human beings into a post-human form that could achieve immortality.
Cody: If you would have said the definition of a transhumanist to me 20 years ago, it would have seemed outlandish. But since then it has seeped into popular culture and it's everywhere. Even if you don't know the word transhumanism, we all know the concept of augmenting ourselves with devices like iphones or watches or implanting medical devices. It's a slow progression into the eventual outcome which is basically that we're an android where it's more and more technology solves the problems we have and enhances the abilities we have. I think transhumanism in my view is really just embracing this pathway that we seem to be on already.
Samira: I went to a very interesting talk a few years ago in which one of the feminist thinkers was giving a talk about transhumanism. One of the things she said that is often the ideas associated with transhumanisms comes from males, is there a female or gender biased kind of viewpoint here? One of the examples she gave was that the idea of transhumanism is actually augmenting our body then isn't that something that many women are doing every day when they wake up and put makeup on and do their hair? That's kind of going with our normal bodies-- that's enhancing our bodies. We put color on it. That's some form of transhumanism by itself.
Cody: Absolutely. Think about breast implants and all the bodywork that gets done in California. They are all part of the club.
Samira: Exactly.
Cody: Max kind of founded it or started it through his writing and thinking. He also founded a company called Alcor which I think is fascinating. Alcor is a place where you can translate your life insurance, pay that out, pay him and his engineers, and then they will cryogenically freeze you at the moment you have been legally declared dead because it's illegal to freeze someone before they are declared dead. They have to be declared dead. Then they will be kept at a super-cool temperature far into the future and at some point in the future we're assuming in this scenario that there would be amazing technology to repair whatever it was htat killed you and maybe even reverse you to a young person. They would eventually wake you up with technology developed to revive cryogenically preserved individuals, fix them completely, and then you'd be a time travele that basically wakes up in the future young again.
Cody: Do you remember going there to see him?
Samira: I kind of also remember my visceral reaction when we walked into that facility. I don't know. It felt cold. I don't know.
Cody: My reaction going into it was that the whole thing seemed a little wacky. I wasn't sure what to expect. What we found I think is actually a very clinical situation. It was very nice. There was a nice medical bay where the bodies are received. I think that's where we should start the conversation with Max actually in the medical bay where they do the operations. There's a CT scanner in one corner. They start to prepare people to be frozen here.
Max More and Alcor
Max: What we're doing is not too different from what a hospital does for donating organs. Actually in fact that's what you're doing. You're donating all your organs to yourself, essentially. After legal death has been declared, hopefully with our team standing by ready because of your warning, we move the patient into the ice bath and cover them with ice. We restore respiration. We need to re-circulate because if you just inject all the medications we use, like the anti-clotting agents, the anti-coagulants, the membrane stabilizers, if you inject them into a body with no circulation then they will just sit there. We try to protect the patient while we get them to the operating room at Alcor. At that point, we cryo-protect the cells and go down below freezing without causing ice formation.
Samira: Right. It's because if the ice forms incorrectly, it can burst open and damage the cells and cause organ damage. That's interesting. How many patients are there at Alcor right now?
Max: We just had a new one. I think it's 157 patients right now at Alcor. It's slowly accelerating. We're averaging around 10 or 11 patients per year. It bounces around though. Eventually it will be tens of thousands per day. Not yet.
Cody: Why do people want to be frozen? Do they tell you their reasons for wanting this? Is there a common thread that has emerged from your customers?
Max: I like to turn this question around a little bit. What precisely is driving people to not want to do this? Why do people want to die when there's plenty of interesting fun stuff to do for the indefinite future? It's the same reason why people will take cancer drugs and have heart surgery, it's because they're not ready to die yet. It's just a little bit more radical. You're essentially in a coma with zero metabolism. It's not much different from being in a long-term coma. The whole idea is that you come back as a young person in the future. You look in the mirror and go, "damn, I look fine!".
Cody: How long do you think these people will be frozen?
Max: Well, that's really impossible to say. I don't believe in nice exponential projections. I really don't know. If you really forced me to guess, then I would say maybe in 100 years. If the AI people are right, then maybe we can solve the problems a lot faster. But I don't know. It doesn't really matter to our patients as long as the organization is sound. We have been around already for almost half a century. Whether it's a day or a hundred years really makes no difference from their point of view. It's so cold, everything is locked down in place, there's no metabolism, it relaly doesn't make any difference. Then you probably start with the easiest patients- the ones maybe cryo-preserved more recently with better technology and under better circumstances. Over time you would work your way back to the more difficult cases ((people cryopreserved with less advanced technologies)).
Samira: Now we are in the storage area. Let's just take a second to describe what we're seeing which is pretty amazing. We are in this large room with high ceilings. It has a dozen filled stainless steel storage pods. The room is bathed in a purple light back in the corner. There are machines that are occassionaly emitting jets of what looks like very cold gas. I have a feeling that reverance- almots like a temple. But if it is a temple, it's not filled with priests but instead I would say it's filled with time travelers.
Max: Welcome to Alcor's patient care bay. We have all 157 patients here. Over here you can see a patient in cooldown. Well actually you can't see them. We have a patient being cooled down right now who came in just a few days ago and the computer is controlling the cooldown rate.
Cody: So the process of waking up a person is probably very difficult as well. Have you tested that on any animals or anything?
Max: Yes, actually, kind of. Very small animal. It's very difficult. We can revive heart valves and skin and embryos. There are millions of people walking around who were cryo-preserved as an embryo. But when you scale up from single tissues to a full human organ, you're already pushing the limits of today's technology. There has been some success in doing that, like the lab 21st Century Medicine in California that we work with, but we're still getting there. Then from organs to an organism is really impossible to reverse at any size. However, we have done it with c. elegans which is a tiny microscopic worm that has been well studied. We first of all taught it a simple memory task. It doesn't have many neurons but we can train it which way to get food. We cryopreserved it after training, re-warmed it after training, and demonstrated in a published peer reviewed paper that yes it does retain its memory. 30 years ago I thought that by now we would have made much more advances but there's no funding for it. I think it will be happen. Will it be soon enough for me?
more cryonics
Cody: Samira, as a medical doctor and also a research scientist, what do you make of cryogenic freezing?
Samira: Well... in research labs, we regularly freeze down cells from animals and bring them back into life. Here I see attempts to replicate these processes at an organismal level. However, it will be very complex to achieve their goal. It requires a lot of research and perfecting of protocols. Having said that, I wouldn't be surprised if in 30 or 50 years from now these issues would have been solved.
Cody: He alluded to that. He is thinking that maybe the way they freeze people today isn't that good and maybe the process will be changed over time as we learn more. But maybe we get so good at this that maybe even the people who were frozen incorrectly today then maybe we can bring them back later too?
Samira: For me one of the crazy things was seeing those individuals who only opted to freeze their heads. What would that existence be like when they wake up? They are essentially comfortable with their whole existence downloaded into a software or a robot? I can't really imagine that.
George Church and longevity
Cody: It's hard to imagine what that would actually be like if it's like anything. One thing that is critical here is that most people actually want to be young again. Another key piece of technology that they need to be developed and revived is the technology to reverse aging. That technology is becoming pretty plausible. One of the pioneers developing that is George Church of Harvard Medical School. He is best known to a lot of people as the guy who wants to bring back the woolly mammoth. But what is he known for in science?
Samira: One of the most important contributions of George to the field has been inventing ways to read our genome.
Cody: I think it's interesting that when he gives a presentation he always puts up his "conflict of interest" slide. He does this to be totally transparent. It's a huge list of companies that he has founded, companies that are based on his patents, his advisory roles, groups that have funded his research, and there's over 342 entries on that slide.
Samira: Oh my god. It's just so impressive. His degree of contribution to the technology and his vastness of vision is admirable.
Cody: So let's go to Boston and sit down with George Church and figure out the reality of age reversal.
Samira: We met George on the stage of the Boston symphony hall. It's a huge space with brilliant chandeliers high above which was an impressive backdrop for a mindblowing conversation with one of the world's leading geneticists.
Cody: Dr. Church, I have a quote that was attributed to you. It says: "As I wonder through life, I'd get that feeling that I've come back from the future and I'm living in the past and it's a horrible feeling." What is the backstory of that quote? What does it mean?
George: I think that mainly- I sort of felt like my brain was permanently wired to think about the future and variations on it that I would invent. You want to be there, you know. It's shinier. It's cooler than what you have right now, almost by definition. It's the greener grass on the other side of the hill. That kind of thing.
Cody: You're known for being a great pioneer in the field of genetics. Many of the technologies you have created have brought the cost of reading and writing DNA down by something on the order of 10 million fold. Now one of the major focuses of your research is now into aging reversal. What do you think the possibilities are?
George: So I'm 63 right now. If you think about how much revolution has occurred in the last 10 years in terms of reading and writing DNA, computing, deep learning, and so forth, imagine whta we could do in the next 10 years and the next 40 years. Just in terms of my own work on aging reversal, we have a paper coming out soon where we cure four diseases of aging with one gene therapy that involves two genes. That's definitely in the direction of where we want to go where we tackle all of the causes of decay and get aging reversal. We know this can happen in animals. I think that's what I am personally focusing on. We do the experiments on 2-year old mice which are almost dead from aging and also 12 year old dogs. If you can make mice last 2x as long as the average mouse with just 3 genetic changes? In principle, if you could reverse aging once, then you could keep reversing and maybe eventually maybe there will be specific problems with one part of your body you couldn't easily replace with stem cells which is the brain which has a lot of connections. But even that, I think we can handle it, and in that case, we can keep applying reversal treatments until an accident happens like an asteroid hits you. I think there's a good possibility that many of the people alive today- not just the babies but also some of the older people- will have the opportunity to greatly extend.
Cody: I've been talking to a lot of people about this. People who have haven't really thoughtfully considered the idea before. Honestly people just look at me strange. They just don't really believe this. It sounds too "out there". If I told them there's a new cellphone coming out or that we would be landing on Mars in 20 years, they might believe that. But the idea that potentially that there are people alive today who will live forever? It just doesn't sound real.
George: Well, I think it- if you say forever then that is indeed unbelievable. But what about 1,000 years?
Cody: If they were sitting across from you at a party, and they said I just don't believe that people will live 1,000 years not even 250 years, how would you convince them that this is very real?
George: Well, it's not my business to convince them. I communicate what I think the ways thing are. We have a huge variation just within mammals. Mice typically live 2 years. Bowhead whales live 200 years. That's just in mammals. It's clearly biologically programmed. And we have species on the planet that live thousands of years. There's nothing magical about 250 years.
Cody: In medicine, there's a colorful history of people testing new drugs on themselves that they invent. Are you testing any of these things right now?
George: Minor. I'm waiting for good clinical testing results for things that my lab has developed.
Cody: Nothing genetically engineered?
George: Nothing genetically engineered, no.
Cody: Yeah. How many years away is that?
George: We hope to have clinical trials in dogs starting now. That will be a veterinary product about 2 years later we could start human clinical trials with the experience we get from mice and dogs.
Cody: So one of the things about George Church is that many many scientists go to George to ask questions about a direction of future technology. We have heard from many people that he is quite good at his predictions.
Samira: At the end of the interview, he mentioned the dogs that he is reversing the age of. That really became a clue for us for where to go next.
Rejuvenate Bio
Cody: George is involved in many companies all over the world. This one is called Rejuvenate Bio. He co-founded it with one of his former students Noah Davidson. Another student named Dan Olliver from Harvard Business School too. They are far along on getting approval to do age reversal therapies for dogs.
Samira: George was kind enough to get us an introduction to Noah.
Noah: Everyone knows George Church.
?: George who?
Noah: Hah. Exactly.
Samira: When you first sat down with Noah and Dan at their offices, they were just concluding trials on the American spaniel. Noah, how did you get interested in longevity research?
Noah: Originally I was in applied physics. Then I joined George's lab to work on aging. When I first met George, I told him I wanted to work on aging and he said "Great, well I'm getting older". And so, I thought it was a really good collaboration from then on.
Dan: I just wanted to do the simple thing of if we can make mice live twice as long then why has none of this information been translated into dogs and people that we care about making them live longer healthier lives?
Samira: Can you tell us some more about the aging process across the animal kingdom?
Noah: The general thing about aging is that you have a very coordinated program to go from a baby to an adult and there are very specific epigenetic changes that occur to turn you into an adult. It's about turning on specific genes at specific times. After you become an adult, there's kind of no more regulation to keep those changes the way they were.
Cody: Dan, how would you explain what you and Noah are doing?
Dan: At different times in your life you're expressing different genes in different amounts which creates certain proteins going on in your body. It signals what's going on. As you age, that balance gets out of whack. With these longevity gene experiments, what they do is keep the mouse in balance longer which then has these health benefits and also the benefit of increasing their lifespan.
Cody: Noah, I'm gathering that the hope someday is to move pass dogs and into humans.
Noah: We're at the step of translating it from mice to dogs and we're doing tests in dogs now. We have proven how safe our therapy is. We're just trying to get the dose right. The next step after that would be getting it into human trials potentially.
Cody: George told us that people may not be able to accept aging reversal yet because we're not ready. So the plan is that you would roll it out with their pets first, let people get used to having that happen safely in an animal they love in their home and this will then pave the path for humans to wnat the same therapy.
Dan: What we want is strong data. There's multiple ways of doing that. Having a therapy come out that really is doing the things we claim to expand healthspan and cure aging related diseases in dogs? I don't see how people wouldn't become more comfortable or excited about it.
Cody: My takeaway is that immortality tech isn't really there yet. But it's one of those things that could develop rapidly. I think it's realistic. My attitude shifted from it being science fiction to thinking it's possible.
Samira: Fighting age-related diseases is very possible. However, I'm not certain enough with whether we can achieve true immortality literally.
Cody: We have been discussing the technology. Just for fun, lte's imagine this did happen. I think people would quit having children. The pressure to have children would decline. You could put it off for 1,000 years because there's no urgency. Maybe we quit evolving because our lifespans get so long that evolution gets frozen. To me it's the opposite of the designer baby problem which is that humans are speeding up and taking control of human evolution. This is the opposite. We have two competing forces on evolution both being created by the same genomic revolution.
Samira: A natural evolution is being shaped by so many variables. We don't know yet what challenges we may face later. There's an immense responsibility to make decisions about what genes we want to change or select for certain genetic diversities in ourselves.
Cody: In the time since we met Noah and Dan, Rejuvenate Bio has successfully completed pilot trials for dogs and they have raised an additional $10 million in Series A venture capital.
Samira: Join us for the next episode where we explore a growing international community of do-it-yourself (DIY) biohackers. This group of amateur scientists are setting up labs in their basements and garages. Perhaps the most influential of the biohackers, Josiah Zayner, is borrowing from the ethos of Silicon Valley and argues for a future without regulation. He thinks that it is the best way to prevent big government and big companies from controlling the future.