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Are there limits to the human lifespan? Is it possible to stop the process of aging? On average, humans now live far longer than at any point in our history thanks to science and technology. On the horizon, advances in new drugs and medical techniques promise a revolution in how we live, age and die. But these advances may come at a steep cost. In this program, experts explore future challenges while debating the ramifications of an immortal society.
This program is part of the Big Ideas Series, made possible with support from the John Templeton Foundation.
BILL BLAKEMORE – NEWS CORRESPONDENT: Humans are now living longer than ever before. In just a century American life expectancy has gone from forty seven to seventy nine years. In one century. Today scientists are growing hearts in the lab, creating organs with 3-D bioprinters, body organs and eliminating cells that shorten life. Eliminating them. Will this new technology yield another dramatic increase in life expectancy? Is it a good idea? That’s a question that some people are asking.
BLAKEMORE: So let me introduce our guests. Our first guest is the director of regenerative medical research and director of the Center for cell and organ biotechnology at the Texas Heart Institute in Houston. Please welcome Doris Taylor.
BLAKEMORE: Our next guest is the director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic and Noaber Foundation Professor of Aging Research. Please welcome James L. Kirkland.
BLAKEMORE: Our next guest is a novelist, a blogger, a syndicated columnist and media commentator and expert in international affairs and biotechnology policy. Ladies and gentlemen: Jamie Metzl.
BLAKEMORE: And our final guest for this evening is the William E. William Davis Jr. M.D. Professor of Medical Ethics and chief of the division of medical ethics at Weill Cornell Medical College, Please welcome Joseph Fins.
BLAKEMORE: And we’re going to start with the question. What is biological aging and why should we study it. Let me start with you Doris.
DORIS TAYLOR, REGENERATIVE SCIENTIST: Well I think biologic aging is really a function of the age of our cells. You know I may, I may act twenty some day but my cells know they’re not. That being said I think biologic aging is really a culmination of stress, emotional, mental, physical parameters that impact every aspect of our body and including not just ourselves, but our organs and tissues.
JAMES L. KIRKLAND – PHYSICIAN, SCIENTIST: I think one of the views in the field is that there are a number of processes which determine your physiologic age or your biologic age as opposed to your chronological age which can be quite the distinct. So when you think of children they’re really quite similar at a particular chronological age you know a kid in kindergarten is very much like another kid in kindergarten and they view a kid in grade one as being a lot older than they are almost the same age as their parents. When people are in their twenties they’re becoming a little more distinct but they maybe at the same level of university and but there are some differences appearing.
KIRKLAND: When you get to people in their eighties and nineties because I’m, among other things, I’m a geriatrician, I see these people. You know many of us are approaching that age in our parents and grandparents have been through this, there are some eighty five year olds who are out there playing thirty-six holes of golf a day and others who have twenty different conditions and are in thirty different drugs. So biologic age and chronological age diverge quite a bit as you get older and really what biological age predisposes to are the major age related chronic diseases. The highest risk factor for having a heart attack for example is your age and it’s more specifically your biological age.
BLAKEMORE: And a brief one sentence definition then of biological age?
KIRKLAND: Well at the fundamental level there are, you can bin or group these processes in various different ways. But one way I simplistically like to think of it that applies across many organisms is a degree of inflammation of tissues, cellular senescence, which we’ll probably talk again about later. Problems with large molecules like DNA, proteins, lipids, sugars and also organelles within cells and then stem and progenitor cell disfunction. You find these processes are highly linked to each other. You use drugs that target one, you tend to affect the others or single gene mutation. And they tend to be conserved across many species although not every process is conserved in all species.
BLAKEMORE: All right. We’ll come back to that. Jamie?
JAMIE METZL – FUTURIST, ENTREPRENEUR, SCI-FI NOVELIST: Because aging is very complex and multi-factorial, it’s really hard. There’s no standard definition of what biological age is. We know, as Jim said, that different people age at different rate. We know that different parts of our body age at different rates. And so while there are these two things, chronological age and biologically, one of the big challenges in this field is to establish some kind of uniformity for what biological age is. And the reason that’s important is because we’re going to talk about these different types of interventions, but we need to be able to benchmark what is succeeding and what is not succeeding. And so biological age, we can understand it conceptually but really making it real in a way it’s going to allow us to compare different types of treatment, that’s the gold standard and we’re not there yet.
JOSEPH J. FINS – PHYSICIAN, MEDICAL ETHICIST: I think age is not just a biological construct; it’s a social construct. And when you start expanding the life cycle and you start interrupting one person’s life with another life in a sequence of generational issues I think we’re going to have to talk about what it means for social disruption. And…
BLAKEMORE: What do you mean social disruption?
FINS: Well I mean you know, you know as a faculty member in a medical school you know the tenure age keeps on going older and older and older. There’s a whole cohort of adjuncts who want my job, right. So. So that’s what happens when you expand the life expectancy of professors. And is that a good thing for the Academy? Or is it a good thing for society? So I think my sense of it is, I’m a big fan of the work that folks are doing here, but I think a useful construct is what we call fair innings. You know that if somebody has a life that’s shortened because of a premature illness and they’re not going to get their full nine innings you want to, you know, extend the life to fair innings. But when you start getting into extra inning games the next day is really difficult when you have to play again. So I just think you need to think about the context, the broader context of what when we change individuals and we change a lot of individuals what are we doing to the group? What are we doing to society?
METZL: I think that’s a really important point about social constructs. Absolutely. But how do we think about what the social construct is? At the time of the Roman Empire the average life expectancy was twenty-five. As you said Bill in the introduction, a hundred years ago it was forty-seven. Right. And everything was benchmarked against that expectation. It’s like in Roman times, ‘oh my god you’ve made it to 40!’ That was like a huge accomplishment. And so I also think we have all of these structures that are just based on this one historic moment. And as things change those structures will also change.
FINS: I think that just quickly I think there’s a question of radical disruption and how fast can you accommodate the change. And the other question is who will get the enhancement?
TAYLOR: I was just going to say that I think a lot of what many of us are trying to do is not necessarily extend life for those extra innings. It’s to extend health through those fair innings. That really the aspects of longevity that we want to talk about are living healthy longer, as well as you know, the kids who call me and say, can you keep my mom alive or the parents who call me and say, can you help my son right?
FINS: And I totally agree but the title of this session is “Engineering Immortality” right? So you know I think we need to understand that there’s a there’s a kind of a medical sort of Hippocratic intent and that how it’s understood that we’re going to live far longer than.
METZL: It’s true. But Doris said in the green room, which isn’t actually green, but death sucks. And I think that we have been socialized to accept death and I don’t think immortality is going to be possible for a very long time if ever. We’ve been socialized to accept death. We’ve been socialized to define our lives in relationship to death. But according again to Doris, death sucks, and when you think of all the wisdom, all the love, all the poetry, everything that goes away when somebody dies if we had the opportunity to extend healthy lifespan, and all of the demographic projections suggest that around 2050 we’re going to start shrinking again as a global public and we would need to change social constructs. But how wonderful if people, people could meet their great grandparents and maybe we’ll have, you know you lose your tenure at sixty or seventy or whatever but let’s solve for that problem. Not say that we have this infrastructure based on our current life expectancy, therefore everyone’s parents and grandparents have to die when there’s a lot of extra potential.
BLAKEMORE: So to get more specific, to move to another topic. Where are we now, you guys who are specialists in this, as far as targeting the aging process?
KIRKLAND: The idea in the field is if we can target fundamental aging processes, can we delay the, can we delay prevent or alleviate this constellation of age related diseases as a group instead of targeting these things one at a time. If you cure heart attacks for example you are choosing to die instead of few months later of Alzheimer’s disease or some cancer. It’s a whack a mole situation. So why not go for these things as a group. As a clinician what I’m worried about is my patients having poor quality of life having onset of these age related disease that cluster within individuals. If you get one age related disease your time for the next one is two and a half years. The one after that is a year. The one after that is six months. They cluster in people. We’ve all seen that. We need to target that and delay it and that’s what some of these drugs do that seem to work in mice. Maybe, if we can get them to people.
BLAKEMORE: I want to ask you about that in a minute. Doris?
TAYLOR: So I think that makes sense though endogenous repair fails and as it fails it doesn’t just fail in your heart, doesn’t just fail in your liver, it fails everywhere. And part of that is because the capacity for repair that we have, these cells come down as we age and those cells, the more hits you take, the more you use those cells the fewer you have the more likely one two three four five set things are going to fail.
KIRKLAND: But I think that’s part of this. I think the other thing that happens is you have damaged cells that don’t, that aren’t gotten rid of so there’s failure to remove cells you don’t necessarily need to replace them in some instances, they’re damaged cells that don’t get removed. They can become cancerous. They can produce things, senescence cells, very small numbers of them produce factors that caused widespread systemic dysfunction. Do if only one in ten thousand of your cells is senescent after, when they’re transplanted, you get, in mice you cause frailty for six months. Causes diabetes,
BLAKEMORE: What happens when you take out senescence cells?
KIRKLAND: Well you get improvements in some of these things. There are there many ways of targeting fundamental aging processes now. There at least you know there are well over a couple of dozen drugs now that target fundamental aging processes in mice and there are many more coming. The question will be, can we say in an older person who’s got five different medical conditions can we improve slightly three out of five of those conditions with a single agent.
BLAKEMORE: Why is slowing or stopping aging a goal? Why is it a goal?
METZL: Well I can answer that in two words. Why not? I mean if we can live healthy, longer that’s just a pure good. And extending health span and extending lifespan are correlated, so even if we say our goal is extending health, and that will very likely, at least in the early years, extend overall lifespan and anybody who’s been at the deathbed of a loved one or a child or a parent and asks the question ‘why can’t we have more time?’ I think that if we can do that if we can that was the purpose of health care is alleviating suffering. And one of the failures of all that miraculous work that’s been done in extending lifespan is that we have more and more people who are in miserable conditions in geriatric centers or wherever. But if we can have people live longer, healthier lives, that’s in my mind just a pure good.
BLAKEMORE: Now you said at the beginning of our conversation, you said something about we’ve been conditioned to accept death. Explain that a little bit.
METZL: Well you’re born and we have all these rituals, and we when people talk about death I would imagine most people in this room would say what’s the purpose of death? Many people would say what gives meaning to life. But would you like to have so much meaning in your life that knowing that you’re going to die two days from now would that really focus your love of your of your life and the answer would be no. So we have all of these rituals and we think about death and we have all these words that we say but if any of us had an individual choice of getting ten healthy years with a parent, more healthy years of a parent or a child then everybody would take it.
BLAKEMORE: Let’s just toss an idea here. I’ve noticed that many cultures have different ways of categorizing and surrounding the notion of death and putting it somewhere safe. People who focus on death who are not trained to do so can get very depressed and it can increase suicide rates in fact. So is there anything, isn’t there something good about having ways to put it off in a safe place? Joe you deal with this?
FINS: Well this great book by Ernest Becker from the seventies “The Denial of Death”, right? And it reminds me of what a European colleague of mine once said about Americans, he says “they don’t die they just underachieve.” And we are a fundamentally death-denying culture. And I think that there’s you know I think no one is against this in a kind of medical way to kind of compress morbidity and decrease the burden of living with chronic disease. But I think there’s a there’s a fundamental illusion of control here that we’re not going to get rid of death. You know it will eventually catch up with us, death and taxes and I think it is part of the human fabric and frankly I think that the fact that we will die gives us some meaning to take seriously the time that we have because it’s not an unlimited gift. We want it to be a little brighter and shinier but it’s not unlimited And I think we haven’t been sold it. It is who we are. And mortality is part of our lives.
METZL: Yeah I agree. I don’t think anybody here is, I don’t think immortality other than downloadable brains, which may or may not happen is what anybody is talking about. But if we can extend healthy lifespan, then great.
BLAKEMORE: But let’s, let’s for a moment. America especially is noted for this you say. What is it about American life that has made us deny death?
FINS: I think it’s extreme individualism. OK. Almost a kind of Libertarianism. Control.
FINS: Control. And in fact the people who seek assisted suicide in say Oregon it’s not pain, it’s wanting to be in control of the timing and manner of their death. Everyone thought it was for pain and symptom management. It’s an existential crisis and it’s a fundamental loss of control and I would say that this is this this effort here is part of that same social urge to have you know control dominion over one’s life, one’s death and how long one lives.
BLAKEMORE: From a psychological point of view, you’ve got new ways of describing to us when it becomes unhealthy to deny it.
FINS: Right, I think, I think what we see this you know in clinical life where people are asking for care that at this day and age is impossible. And you know issues of medical futility. Interestingly the word futility comes from the Latin futilis which means a leaky sieve, you know it no longer serves its purpose, it doesn’t hold the fluid. And you know it’s amazing how we seek to extend life. And people just can’t accept the finality of it and it leads to tremendous grief. And so you know I think we have to be less dichotomous about this and appreciate that there’s a benefit here in compressing morbidity but we’re never going to get rid of our mortality.
TAYLOR: I think we have to talk, to continue to talk though about quality because, because a number of the medical devices that exist at least in the cardiovascular field, there are a lot of people who would say ‘yes I want a device and I want to live longer.’ And they get that device and they realize the quality of their life is not as good as they thought it was going to be and all of a sudden the conversation changes. And I think we have to be able and willing to discuss quality. And I mean you see it, this it what you do. Don’t you deal with people who have quality issues all the time?
FINS: Yeah, as a geriatrician what I see is what people fear the most is loss of independence and control. And, you know, myself and my colleagues in geriatrics were sick of providing better wheelchairs, walkers and incontinence devices. So finally the biology of aging in the last, you know, since around 2009 has moved very quickly to developing interventions where we might be able to enhance healthspan even if it’s a few months or a couple of years or something like that. It would probably add a lot more in some ways arguably than curing heart attacks because if you cure, if you cure heart attacks you’re choosing instead to die, as I mentioned before of Alzheimer’s or some horrible cancer, because these conditions cluster. So our goal is to figure out a way to delay these things as a group, even if it’s a small amount, and to try to compress morbidity. And these are potentially achievable goals over the next decade because we can do it now in mice and other lower mammalian species. And the question is can we get this to people in an incremental way, in a safe way where we’re dealing with targeting multiple conditions at once instead of one at a time.
METZL: And that’s a really important issue because right now we have a fundamental problem of the misallocation of resources. We’re doing what Jim called the whack-a-mole. Maybe somebody has cancer you go after the cancer. Then they have cardiovascular disease, we go after that. But if one thing, if we eliminated all of these diseases even then people wouldn’t live that much longer. But if you get rid of one get rid of all cancer in the world it’s about 3.3 years extended lifespan. And so the question is why are we spending so much on the diseases of aging and so little on understanding and targeting aging itself.
FINS: Which is the main risk factor.
METZL: Yeah exactly.
FINS: The upstream cause in a way of these conditions
METZL: So right now, and every one of these diseases are, they’re all terrible and they all have pressure groups and they all have an infrastructure for cancer, cardiovascular disease, dementia, whatever. And what needs to happen, at least in my view, I think some people up here would share this view, is we just need to shift some of that spending into understanding the basic science of aging. Because from an evolutionary perspective, we all, everybody has this sense of what is and isn’t natural. But the things that we think of as being natural actually aren’t natural at all. It’s not natural that we live to 80, its just that our ancestors didn’t do it, it’s this one is the period of time. There’s nothing about evolution that has decided that we live to 80 because frankly evolution could care less how long we live. If babies are getting eaten by tigers babies would grow armor. If parents were getting eaten by tigers and they couldn’t raise their babies, babies would become more independent like Komodo dragons do. But if an old person got eaten by a lion, it was bad for the old person but it didn’t really touch our evolution as a species. So there’s a lot of fluidity in how we’re going to be able to age, in my view, how we’re going to be able to impact and target the mechanisms of aging and animal models are showing as you guys has been mentioned that there are a lot of things that that can be done and I think should be done.
TAYLOR: But I want to speak about animal models, I feel really strongly about this. We can cure anything in mice. We can cure cancer in mice. We can cure aging in mice. We can cure heart disease in mice but we can’t cure any of it people. And that’s because those animal models are healthy until we give them a heart attack. Or they’re healthy until we do whatever. We don’t have models that let us look at old, sick, taking all these drugs, also have cancer, also have all these other things. Models where we have to test these things.
TAYLOR: So I think part of really figuring out how these work is testing them in real life situations. And I think it’s important to understand women live longer.
KIRKLAND: It varies across species to the gender differences so that female mice don’t outlive male mice.
TAYLOR: They do if they have heart disease.
KIRKLAND: It is very situation dependent. Generally female mice have the same life span as male mice. In other, some other species males outlive females for example and some birds. So this varies and it’s peculiarity.
KIRKLAND: What, one thing that does seem to be fairly constant are some of these fundamental aging processes from yeast through worms, through flies, through mice. Unlike something like Alzheimer’s disease which is a uniquely human disease or unlike arteriosclerosis, which is almost uniquely human, does occur in some other species. Aging, fundamental aging processes tend to occur across species so there’s some hope and I think we have to have a lot of skepticism as you’re saying until we do clinical trials. There’s some hope that they might be translatable. But as you’re saying we have to do the clinical trials and we have to show this in people because you know showing things in mice or rats or dogs or monkeys doesn’t necessarily translate.
BLAKEMORE: Let me see if I can get my aging brain just to summarize what we’ve generally been saying so far. You’re saying that more than going after individual diseases, go after aging. That’s what you all are saying.
BLAKEMORE: What is, what is the future is it regenerative medicine? Or is it a new kind of medicine?
TAYLOR: I think, I think it depends on what you’re trying to do. If you walk in the door and your legs. you’ve cut off your legs at the knee and you’re bleeding everywhere obviously you have to deal with that first before you can think about how old you are and what you got to do. And I think I think some of the disease states that we’ve been talking about heart disease that you know other chronic diseases we have to get under control. And as we develop new hypotheses about aging and understand aging.
FINS: I think there’s two things. I think this falls generally under the rubric of prevention. Right
FINS: But it’s a kind of secondary prevention. After you know that process has already begun. People who were you know in their forties may not have had a heart attack but they may have arteriosclerotic changes and could you reverse that for some you know anti-aging intervention versus an earlier public health intervention that that changes the built environment, puts calorie counts on the food, teaches people about you know high fat diet. So I think it’s important to realize the built environment has a lot to do with the process of aging. Some of it’s going to be genetic; some of it’s going to be environmental. This is all under the rubric of a kind of prevention and I would hate for people to think they could they could live whatever life they wanted to live and then when they’re 45 they could go check into the anti-aging clinic and get some kind of magic bullet. When if fact it’s better to have a kind of a multifaceted approach to prevent any morbidity that’s downstream.
METZ: What’s the biggest intervention that I can do right now because I really want to live as long as possible? It’s all these things. You need to eat healthy. You should exercise 45 minutes a day. Don’t smoke. There’s a lot of work on what they call Blue Zones, which are part of the world where people live longer and Dan Buettner and others went and said well what do they all have in common? Is it that everybody had that physical activity built into their lives, they were in communities? They had a sense of common purpose and for whatever reason they ate they all seem to eat a lot of beans. But having said that everybody should do all those things. But it’s also true that in some of the metformin studies for example they have the two groups of mice. One with mice the they ate crap and didn’t exercise. And one with the mice that they ate good food and exercised. And they gave metformin to the non-exercising, lazy, fat mice and they outlived the healthy mice, so I think that you should do all of those things. But then there will also be very likely be in my view other types of interventions, that you’ll be better off if you lived a virtuous life, but will help everybody.
TAYLOR: It’ll feel like you’re living for seven thousand years if you’re only living a virtuous life, right?
METZL: Which some of us enjoy.
KIRKLAND: Some of these interventions will see their first light in early clinical trials in roughly a half dozen areas. And some of these trials are under way at the moment. So one of the areas is going to be looking at multi-morbidity. So if you’ve got an eighty five year old who’s got five or six different conditions, can you partially alleviate three of those conditions with a single agent? So that’s one approach. The second is going to be in conditions where they are accelerated aging like states. So trials are beginning and people who have bone marrow transplants and have massive doses of chemotherapy and acquired this accelerated aging like state in three to five years, or the kids with progerias who look old when there when they’re young. Another area is going to be where there are localized accumulations of changes that are associated with aging like states for example pulmonary fibrosis, idiopathic pulmonary fibrosis which is normally fatal without a lung transplant. Again we at Mayo recently published a paper showing that these drugs that clear senescent cells radically improve mice in that particular model and clinical trials are going to begin.
BLAKEMORE: On humans.
BLAKEMORE: How soon.
KIRKLAND: Very soon.
KIRKLAND: Will these kinds of drugs reduce the amount of chemotherapy that has to be given or reduce side effects of chemotherapy or enhanced recovery after surgery or enhance recovery after pneumonia? Will they, and some of them do this now, one trial’s already been done showing that we can improve vaccine response in elderly individuals to flu vaccine by giving these kinds of drugs, in this case a drug related to something called rabomicin, for a few days two weeks before they got their flu shot. And these were communing, living, healthy elderly individuals who normally have bad response to flu vaccines, and it was greatly improved by targeting fundamental aging processes. So there are a bunch of clinical trial scenarios that have been gained out over a three-year period by a large group of aging centers across the country and involving Europe that included the NIH and the FDA. And so they’re very short-term trials that could be done in a short period of time with subjects involved in the trials for two to six months to look at these kinds of interventions and see if they work and those trials are beginning.
BLAKEMORE: Well this comes to the next question I wanted to ask about, is have all of you give us a sense of what the next twenty or thirty years in this field look like. Where are we going?
METZL: Well, I’m the only science fiction writer here so I feel the freest to just make stuff up which I will do. So I think in the near term, I’ll do it in three buckets, in the near term all of the kind of work that we mentioned to this point, I think some of that will bear fruit. Some of it seems very promising now and it turns out it won’t work. But there will be a lot of things whether it’s rejuvenating stem cells or pruning senescent cells or using blood plasma transfusion to trigger certain cellular responses or all kinds of small molecules. I mean a lot of these things that are undergoing, some of them will be realized. That’s the short term
METZL: In the medium to longer term, I think things are going to get more…. It’s going to be more, maybe ethically challenging and the kinds of things which people, I think everything about these interventions, my guess is most of you in the audience will say well that’s pretty good if I’m aging and you can do this kind of an intervention. But in the medium, in the medium term we’re going to use genome sequencing and we’re going to understand different genetic combinations that give you a greater shot of living longer. I have written a book on the future of human genetic engineering and embryo selection but I think that there will come a time in the not so distant future when all children, the majority of children will be born through IVF and those embryos will be screened and they will be screened for certain outcomes. And your possibility of living a long and healthy and robust life will be one of those outcomes that will be screened for at the time when decisions are being made about which embryos, early stage embryos to be implanted in the mother. That would I think that is medium term.
METZL: And longer term, if we’re talking hundreds of years, and again I’m a science fiction writer so take this with a grain of salt, if we do get to the point of downloadable memory and we can transfer our minds into some other medium then we’ll just have this fundamental question, ‘is that us’? So if somebody has today has locked in syndrome and the only way that they can communicate is with their eyes you would say is that a person? I think the answer that everybody would say, the answer to that is yes. But if you said that if you transfer that person’s brain into a functioning robot and now that person could walk and speak and do all of the things that they couldn’t do when they had locked in syndrome is that the same person? It’s an ethical question but at some point that may be the kind of life, if we’re really talking about immortality, that may be the question or asking.
BLAKEMORE: I sense all kinds of potential red flags going up in the back of my brain.
METZL: As you should.
BLAKEMORE: And in the front of Joe’s.
FINS: Well you know I think but let’s start in the short term. I think you know the history of medicine is littered, you know, with the more failure than success. And so you know the classic immortal cell is the cancer cell.
FINS: OK, that doesn’t stop dividing. So I think that the risk of iatrogenesis and doing harm, Primum non nocere, above all else do no harm to be probably at the forefront. I think the skepticism about translating from animals to humans is indicative of that concern.
FINS: You know longer term I think that that there are issues of social disruption you know changes in longevity, health disparities I think are a really big issue. There’s a concern about you know changing expectations, the science getting ahead of social norms, social constructs and this would be a classic story that we do all the time. We have a scientific advance and then we’re trying to catch up with it. You know we have a hard time with genetic testing. And I’m worried about sort of the eugenics, you know, flavor of selecting embryos. I think we’re you know we’re strengthened by our diversity and there are many people in this room who are probably heterozygote for something bad. I would say everybody in this room is heterozygote, have a good gene and a bad gene you know. So if we were selecting for that for the good genes, a lot of good people will be left out. And I think that that really worries me and that hasn’t worked out too well with history.
FINS: So you know and again last point, you know all these people cite enhancement. People who are in favor of enhancement, the philosophers, some of whom were mostly in Oxford you know, are the people who need to be enhanced the ones who were going to decide how we’re going to be enhanced? Again it’s the humans. So I’m very concerned. I have no trouble with the medical you know utility compressing morbidity and improving the life span and I think that’s all terrific. But I start worrying about us engineering our future as a species in a way that’s incredibly disruptive.
BLAKEMORE: And this comes in the field of new understanding of post neo-Darwin thinking about what evolution is. The old view, which was not Darwin’s, was that it was just simply random mutations and struggling for survival of the fittest and fighting tooth and claw. The new view, from what I understand from what I’ve been reading lately it’s much more complex that we are a species that gets ahead by not just by having winners or losers, but by cooperating. A lot of cooperation and sharing is what maybe makes us so much.
KIRKLAND: Plus epigenetic factors there are environmental factors, which are not inheritable.
BLAKEMORE: Right. So Lamarck was right. Acquired characteristics should be inherited. So this leads to a very difficult, I’m glad you used the word eugenics because we should be reminded eugenics was very popular in America in the tens and twenties and thirties and then when they were sterilizing people who seemed to be imbeciles and a lot of that was going on legally. Eventually became illegal. But people who liked it went over and joined Hitler’s groups who carried out experiments in Auschwitz for example.
METZL: Yeah but I think the science is advancing and the science, it’s not coincidental that Jim was talking about that big advances over the last decade. We are at an inflection point in our science and we are at an inflection point in our evolution as a species. And so for four billion years our ancestors have evolved by the forces that you that you’ve mentioned. But right now our science is beginning a process and of allowing us to guide our own evolutionary path.
FINS: Utopian thinkers have been saying that for centuries.
METZL: For sure
FINS: It’s not a new story.
METZL: Yes, but our tools are so much more advanced
FINS: And they’ve been saying that too.
METZL: And that they’re getting more advanced. And so but we will still have the same ethical challenges.
TAYLOR: But the decision-making has not gotten more advanced is what I was saying.
FINS: We’re still human.
TAYLOR: And the people who are in power and the people who are making those decisions have not necessarily gotten more advanced either.
METZL: That’s one hundred percent correct.
FINS: In fact we’re in a post-Enlightenment age…
METZL: We are we are heading in the wrong direction.
FINS: We don’t believe in fact, we don’t believe in science.
TAYLOR: We don’t believe in vaccines.
METZL: There’s no doubt about that.
FINS: A plus B equals catastrophe.
METZL: I agree. I completely agree with that. And yet the science is advancing exponentially and so the onus, that’s why these kinds of conversations are so important, is the onus is on all of us. Because you can either stop the science and let’s say you stop it here it’s going to happen someplace else or you can say well we better really get our act together and if we value diversity, let’s have a conversation about diversity
TAYLOR: Back in the 90s I was doing stem cell research when, when then President Bush said we’re going to we’re going to eliminate embryonic stem cell research. And I remember getting called by the media and asked how I felt about that and I basically said the problem is, if we’re only going to use the established cell lines that were all established from rich white people who can afford in vitro fertilization, guess what? We’re only really about twelve of those that are any good. So we’re going to make all our decisions about stem cells going forward based on twelve rich white people? That scares me because diversity is what we need to understand biology. If you look at every one of just us, who aren’t that diverse, we’re going to be different.
KIRKLAND: Another axis of diversity is people who have disabilities.
METZL: I couldn’t agree more about diversity. Diversity is our sole survival strategy as a species and has been from this from the beginning. So if we lose whatever people think is good, it’s good now it won’t be in in the future. And with these ethical questions that’s at the essence of the debate that everybody needs to be part of. This is not a debate for experts it’s not even a debate for just one for one day or one weekend. I mean these are the questions are the fundamental questions about the future of our species. And that that should be the top of everybody’s minds. But we can’t close our eyes to where this technology is heading because again we could shut this down in the United States. It will be good or bad whatever your views are for the United States but it won’t have any impact whatsoever on the advance of this technology.
TAYLOR: The fact that reproductive cloning happens. The fact that CRISPR technologies that you’ve all heard about where you can you can actually, you can actually edit someone’s genes in real life says, and it is happening in humans outside the US now, is something we all ought to be discussing and what we, whether we embrace that or don’t.
METZL: And if you had a time machine and you went a hundred years into the future and people were saying, oh we have this thing, it’s made of code. The code is writable, it’s readable, attackable you’d say oh yeah I got you. It’s computer code and they’d like look at you like you’re crazy. No it’s biology right? We are we are developing the tools to write and rewrite the code of life. We may be wise or not wise in those applications but we will have those tools.
BLAKEMORE: And forgive me for asking this question, but we’re talking about people who are lucky enough to know about all this stuff. Do you think it will be something that can be spread to all humans everywhere without a lot of the expense eventually?
BLAKEMORE: Or will leave a lot of humans just dying and in terrible health?
METZL: I think that again it depends on what our values are. Right now we have all of the food to feed everybody on Earth. We have the clothing to clothe everybody on Earth. We choose not to do so. If we maintain the bad values that we collectively have now that will be the case. But there is, there are financial incentives because eliminating, as Jim was saying, if we can eliminate or reduce the occurrence of these co-morbidities associated with aging that’s going to be a huge amount of savings. If people are living healthy hundred year lives and then and then die relatively quickly, that’s going to free a lot of resources that can be invested in all sorts of things.
KIRKLAND: There’s a phenomenon, there are people who are what we call super centenarians. These are people who live to a very advanced age that tends to be inherited in families. And one of the interesting things about these people who are dying at one hundred and five, one hundred and ten, is that when you look at large numbers of them they live very, very healthy and independent and they tend to be dead within six months of their first visit to a doctor, so they die very quickly. We also notice this in experimental animals that are treated with some of these kinds of interventions where a single gene mutations have been used that have an effect on lifespan.
KIRKLAND: There are also some data from about twenty years ago that came from studies of health utilization. That the last two years of life are the most expensive. They’re three, the last two years of life of a person who dies at seventy cost three times the last two years of life of someone who dies on a hundred. And that may in part because of this rectangularization of morbidity. So I’ve got a shorter-term view of some of this. I’ve got patients here now. My view is I want to extend their healthspan and delay the onset of these diseases. And it’s turning out now that these interventions will actually treat some of these diseases once there’s established including fragility, in animals.
BLAKEMORE: Sorry to interrupt. Healthspan. You’ve used that term twice. A lovely phrase, healthspan as opposed to lifespan.
KIRKLAND: Yes, so healthspan is a period during life when people are living independently, free of pain, free of disability. You know basically able to do what they what they want to do. So the goal of the field, as far as I can read it from my vantage point, is that we want to improve healthspan and if lifestyle is increased that’s a side effect.
BLAKEMORE: So a question about the fact that these things seem to run in families, parents, grandparents going back that way. But is it necessarily something that runs in families because it’s passed down genetically, or genetically and epigenetically, or both of those plus culturally, and just something about the lifestyle?
KIRKLAND: This has been noted across populations in different countries and I’m talking about people who live beyond, way beyond a hundred. So there are several trials looking at these kinds of populations going on around the world. There’s a high heritable component but it’s not everything, so of course they’re going to be epigenetic and social and other kinds of factors involved. But some of the genetic changes that account for or contribute to this increased longevity within families are beginning to be worked out. There are about a dozen, a dozen polymorphisms we call them that have been found so far and they make sense because they follow the same pathways of food restriction which extends lifespan in many species and they contain the targets of these kinds of drugs that are being developed that affect lifespan.
BLAKEMORE: So that sounds hopeful. Eventually you may be able to get to understand this well enough to be able to spread the knowledge to everybody.
KIRKLAND: That’s the idea. And as we were talking about before, some of the early drugs that may have an effect…and don’t take these drugs. Don’t take them. We haven’t done the trials yet. Don’t take these drugs.
FINS: They’re all taking their paper out.
METZL: It happens every time somebody says where do I get this.
KIRKLAND: Don’t don’t. Some of them are very, very cheap like Metformin we were talking before, two to five cents a pill. So if we are able and in the next iteration after we do these short term kinds of studies and look at individual indications and see if they in aggregate line up, with the possibility we’re targeting fundamental aging processes, we may move to kind of preventive strategy. And if that happened to work, if that happened to work, it would by projections that have been done by a variety of groups, reduce health care costs enough that the intervention itself would be relatively much cheaper for any society.
FINS: Could I just, Maybe you guys could just talk a little bit about the role of inflammation in aging because I think that that would be really interesting to kind of get on the table.
KIRKLAND: Well chronic, what we call sterile, that is in the absence of bacteria or viruses, low grade inflammation is something that you find in many tissues and sites of age related disease. So this is where immune cells go and release factors that cause dysfunction. Senescent cells act in part by producing a lot of inflammatory factors and also attract cells from the immune system in. And these kinds of factors will also poison stem and progenitor cells and cause them to dysfunction and can contribute to macromolecular dysfunction comes with DNA and proteins so all these things are sort of interlinked. But this kind of inflammation is very special inflammation. It’s not the kind of inflammation you would treat with a non-steroidal anti-inflammatory drug or with aspirin. Although aspirin does in mice and related drugs, salicylate, does have some effect on median lifespan at least in lower mammals.
KIRKLAND: What we’re talking about is inflammation that’s much more specific and of a particular type and Metformin is one of the drugs that targets that kind of inflammation, rapamycin is another one that does it. So these are these are inflammatory mediators produced by senescent cells, something called senescence associated secretory phenotype. Long word, we call it SASP. That form in part works by targeting that pathway.
TAYLOR: So I want to speak to that though because I, my worldview is slightly different which is that acute inflammation is a good thing. Acute inflammation is when an injury occurs and basically your body is producing a signal saying ‘hey there’s an injury’, and I need repair, whatever that repair happens to be. And I happen to believe part of that is these cells that you recruit, they’re not all stem and progenitor cells, some of them are immune cells, so you get those cells there. A number of years ago we started look….and if you get those cells there you turn off the inflammation. If you don’t, your body ramps up inflammation and I think it’s like your body saying ‘I said I’ve got an injury send me cells!’ And you start recruiting the wrong cells and getting a secondary pro-inflammatory effect.
TAYLOR: A number of years ago we started when people started doing stem cell therapy trials, that were primarily bone marrow derived stem cells, many of you may have heard you get bone marrow from your hip, you take the cells and you give ’em and you’re giving stem cells. Well only three percent of the cells in our bone marrow are stem cells, the other ninety seven percent are not stem cells they’re immune cells or other types of cells that are going to give rise to blood cells or etcetera. And when we started measuring those and said which cells that are present associate with repair, guess what? It wasn’t the stem cells, it was the immune cells. So there’s a whole response to inflammation that is, I mean, stem cells and the cells we give turned down inflammation reproducibly acute inflammation is great long term
BLAKEMORE: In a moment I’m going to open this up to questions from the audience.
BLAKEMORE: But I want to ask one question, is it possible that that death has an advantage for the evolution of the species because it means the young have to take over at a more frequent rate.
KIRKLAND: There are some situations where that’s true. To use technical terms, there are three kinds of late life history. One of them is no senescence basically or no sort of classic biological aging. And the other is what we call semelparity that means giving birth once and another is iteroparity that means giving birth multiple times. So in some plants and some animals if you do the right things evolutionarily or the environment changes the right way you will find individuals die upon reproduction. So dandelions do this and a lot of annual plants do this. Pacific salmon species do this, where the rainbow trout, which is actually a salmon, doesn’t. And so very quickly in evolutionarily terms, you can turn a species from being an iteroparity, it is giving birth multiple times and then having a senescent phase and dying, to dying upon reproduction. And you do that one of the ways you can do that in fruit flies which normally are what we call iteroparous you can make them semelparous and force evolutionary experiments in the laboratory by restricting their food.
KIRKLAND: So there’s an advantage to having post reproductive individuals die very quickly under that special circumstance and you can find a cause of death. For example in salmon they get massive production of corticosteroids from their adrenal glands which kills them after they start, after they spawn, upon going up a stream. You remove their gonads and their adrenals and they’ll live twenty years instead of two to four years. So it can happen.
BLAKEMORE: So this raises this sort of gives us new framework to think about where we may be going with the science that you all are specialists in. If we, if you’re giving us, as humans the choice about what we want to make our particular lifespan we might choose to want to have necessarily a younger generation take over every one hundred fifty years.
METZL: Well two points to that. One just to follow up on Jim’s very interesting point. If you want to live longer eunuchs live longer than non-eunuchs
TAYLOR: Women who get pregnant one two or three times actually live longer, beyond three times mortality goes up. It’s a J-shaped curve for mortality.
METZL: Yeah and I like to put in a plug for wisdom. I mean again there was some recent research about killer whales where they found out that it was the oldest woman in the pod was the leader because she had she had had all this information that had been stored up over the years, so if we have a thing where people are living longer then that’s great. If we have a social issue of tenure or whatever, let’s solve for that issue. But, how much investment goes into every human, a lifetime of experience and knowledge and if we could unleash that capacity of all these older people who now are having dementia, they can’t communicate and they can share and we find a structure that allows us to have any….
TAYLOR: Let’s go back to the Blue Zone though, it was community that associated to the greatest degree with longevity.
BLAKEMORE: Alright. Questions.
AUDIENCE 1: There are some futurists who think that the singularity is near. Namely that we are approaching the stage where AI, artificial intelligence is going to take over. It’ll become more involved than we are. And some of them, Ray Kurzweil, for example, you know think that that is really near. So it is possible that biological intelligence is a relatively short lived phase in the life of civilization, only to be taken over by some form of AI
BLAKEMORE: Any thoughts here?
METZL: Let me be the first to respond to that and just because like I said I’m a science fiction writer. My last book Eternal Sonata has a blurb from Ray Kurzweil on the cover. And, but what he means by Singularity is just that machines become self-replicating and so that doesn’t necessarily mean that the machines will take over. It just depends on what the code says. So we better write that code carefully but you can choose Yeah.
AUDIENCE 1: Consciousness
METZL: So we will for sure, our biological evolution is a way station in our overall evolution. We will call co-evolve with our, we are already co-evolving with our technology. We will continue to evolve and we will become a hybrid species. That doesn’t mean we won’t have values that doesn’t mean we won’t be asking these ethical questions but we are going to have to do it in the context of a changing world that will be very much but not entirely driven by technology.
AUDIENCE #2: if you have heart disease. Maybe you could change your heart or maybe you could change your kidney. But I could see a limitation related with your brain because I can see the cells in your brain are different. You can’t regenerate these cells. So you know like when you when you are 60 years old, or around this age, they can get the process started to go down. So it was in the future about immortality brain is burden. So what is happening right now? How in the future could you improve your brain?
KIRKLAND: These drugs are improving cognitive function in old mice.
TAYLOR: It’s the same story different target organs, you know it, it’s all there all, all of our organs are affected our brain just the consequences are different.
FINS: And there’s been cognitive enhancement using deep brain stimulation in Parkinson’s disease in some patients as well.
TAYLOR: And stem cells for traumatic brain injury and stroke.
METZL: We haven’t talked to that parabiosis but that they have these things that these people have been doing for hundreds of years actually. We get an old mice old mouse and the young mouse you cut it open and stitched together. And then after over time the old mouse becomes young in many ways the young mouse becomes old in many ways and it’s skin it’s muscle but also, sadly for these mice because it’s not pleasant, but when they biopsied their brains the young the old mice’s brains have become younger.
TAYLOR: So pregnancy is the ultimate parabiosis. And that’s part of why we think that there is a benefit for a few pregnancies because you share all of things but then over time the stress of pregnancy, it wins.
METZL: It’s the thing, we all, it makes sense intuitively to people that you’re like an adult and you can have a baby But it’s when you think about it it’s like that’s really weird. Like I’m whatever thirty years old and then you’ve created a thing that’s zero.
TAYLOR: And that’s why women’s immune systems have to be different and inflammation is different.
FINS: Its meiosis, the genius of meiosis right that rescrambles the deck and its not engineering.
METZL: So we have that capacity within our selves.
BLAKEMORE: All right his gentlemen right here.
AUDIENCE 3: This might be for Jim, but there’s a lot of impressive research going on in terms of regeneration of tissue and organs. But I was wondering, you know, is the population just predisposed to have a certain percentage of people with Alzheimer’s? What’s being done with gray matter in the brain during the expanding quality of life?
KIRKLAND: Well funding for Alzheimer’s research has taken off recently. That is an area where there’s been a considerable injection of funding. And the areas has become, I mean under the surface there’s a lot more progress being made than people realize that there’s a very interesting clinical trials one of which they’ll be some results from next year so that that field is moving faster than I think the public realizes. We have to bear in mind that the brain is part of the body is not a separate thing. And so some of these processes that affect other organs or have general systemic effects are also going to affect a predisposition to Alzheimer’s and related disorders. But I think a lot could happen soon. I hope
BLAKEMORE: This gentlemen in the back who is so patiently waiting.
AUDIENCE 4: So to circle back to kind of what we’ve opened with, talking about where the last hundred years have gone in terms of age, what is the community or individually your personal opinions about where the next one hundred years will leave us or you know what are you going to expect the numbers to increase to?
BLAKEMORE: Let’s get an answer from each of these panelists and that will be the way then we’ll end. Doris?
TAYLOR: My sense is that that tools are going to get more, tools are going to get cheaper. Hopefully we’re going to disseminate things more broadly. And the ethics are going to have to come in to it.
KIRKLAND: I think once you go beyond five your predictions you start getting into a muddy water by ten years, you’re often wrong. By twenty years predictions, you’re just about always wrong. So I hate to think of making predictions about what will happen a hundred years from now.
METZL: I’m in the business of making predictions about what’s going to happen a hundred years from now I’ll take a swing at it. So over the last hundred years an average lifespan has extended by three months per year. So let’s just say we keep that going for another hundred years. Then that’s plus twenty years of average life expectancy. I think again we look at the exponential increase of all of these technologies with biology becoming information technology in a hundred years, the amount of change between now and a hundred years from now will be fifty, sixty, a hundred times more than the change over the last one years, and that’s only going to get faster. So I again I can’t say specifically what’s going to happen but we are going to see life and biology and a lot of things very differently in a hundred years than we do know.
KIRKLAND: One of the things to also be cautious of is scaling. So although we can increase a mouse’s lifespan by seventy-five or eighty percent, that translates into a certain number of months, you know when. If we go to people, would we, would we have an effect on life or health span that would be a seventy-five or eighty percent increase or would it be a ten-month increase. So there are a lot of scaling issues.
FINS: Go online and look at a medical journal from 1917 and read how confidently they thought that there new innovations, what they were going to do for our generation. And I think with that that sort of retrospective does, it gives us to give us all a sense of humility, great encouragement of the promise of this work, but going forward with a sense of humility about the mystery and the complexity of this biology that we’re just beginning to unpack.
METZL: And yet when you compare the whole suite of technologies available now to one hundred years ago it’s unimaginable. And so I think…
FINS: A hundred years from now there will be a panel just like this and a guy just like me and a guy just like you and we’ll be having the same debate, I’m sure.
METZL: No, but this guy is going to be plugged into the cloud and have all kinds of super intelligence
TAYLOR: So what that argues is that technology continues to increase like that, biology is kinda, a lot slower.
METZL: But I think \ those trend lines are going to merge. They we’re going to turn, as I mentioned, our biology into a form of IT and then all bets are off.
BLAKEMORE: We’ll I’d like to acknowledge that we’ve had an astonishingly great panel, great depth of knowledge and the experience.
Are there limits to the human lifespan? Is it possible to stop the process of aging? On average, humans now live far longer than at any point in our history thanks to science and technology. On the horizon, advances in new drugs and medical techniques promise a revolution in how we live, age and die. But these advances may come at a steep cost. In this program, experts explore future challenges while debating the ramifications of an immortal society.
This program is part of the Big Ideas Series, made possible with support from the John Templeton Foundation.
TOPICS: Art & Science, Biology & Origins of Life, Earth & Environment, Kavli, Mind & Brain, Physics & Math, Science in Society, Science Unplugged, Space & The Cosmos, Technology & Engineering, Youth & Education
Video Duration: 00:59:50
Original Program Date: Friday, June 2, 2017
James L. Kirkland, M.D., Ph.D. is the Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. He is a Board-certified specialist in internal medicine, geriatrics, and endocrinology and metabolism.Read More
Joseph J. Fins is The E. William Davis, Jr. M.D. Professor of Medical Ethics and Chief of the Division of Medical Ethics at Weill Cornell Medical College where he is a tenured Professor of Medicine, Professor of Medical Ethics in Neurology and Professor of Health Care Policy and Research.Read More
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