2018-01-21 Chat with Aubrey de Grey
Duration: 00:29:38
Transcript
David Deutsch
I’m sure you’re right. In your own map of things that have to be done before we can engineer negligible senescence, which of them is the most challenging scientifically and the one you’re least sure we can do?
Aubrey de Grey
Definitely the combating of mutations in our nuclear genes, in other words, our chromosomes in the nucleus. That doesn’t have to be done thoroughly, but it has to be done in a way that stops us from dying of cancer, which is the hardest part of aging to fix. The reason it’s the hardest is because, unlike everything else that goes wrong with us as we get older, cancer has natural selection on its side, so to speak, and the cleverer we get at throwing new treatments at it, or indeed the cleverer the body gets at doing so, the cleverer the cancer gets. It’s very, very hard. The approach that I’ve outlined for doing this is extremely ambitious. It’s still something that we ought to be able to demonstrate within the next 10 years or so in mice, but maybe another 15 or 20 years from now.
David Deutsch
Right, and now suppose that that works, and suppose that the other elements of your, what you call the roadmap, suppose they all work out, how confident are you that the net result of that will indeed be negligible senescence, that in other words, how confident are you that after that there will be another series of things which are killing us and which we’ll have to start again from scratch and so on?
Aubrey de Grey
I’m not at all confident of that. In fact, I’m confident of the opposite. I’m confident there will be other things, but I’m pretty confident that they won’t kill us for at least another 30 or 40 years. The reason for that confidence is that there’s already quite a bit of variation in the rates at which the things we know about accumulate in different people, and also in different people some things accumulate faster and some slower in the same person. So that inherent variation that we see in the population tells us that things that we haven’t yet spotted, even though we’ve been looking quite hard, are unlikely to become prevalent until we reach maybe 30 or 40 years older than we currently are. Now, of course, we’re still going to fix them by then, but that’s quite a long time in technology, so I’m hopeful that we’ll be able to do so. And furthermore, I’m fairly sure that if these things that are coming up behind us are elusive and so hard to find, then probably the best way to find them is to eliminate the things we do know about and thereby unmask these other things, even if it turns out that those other things are much harder to fix and we don’t fix them in time.
David Deutsch
Right, but in any case it’s not a matter of one more hurdle, it’s a matter of crossing the barrier that we know about and then turning around and doing it again, except with the new one. That’s right. Right, yes. Now, you said the most challenging thing you said is basically curing this particular cause of cancer. So it seems to me then that curing diseases, that is the conventional aim of medical science, is going to be needed. And also every bit of progress in conventional science is going to contribute, is going to increase lifespan and therefore contribute towards your project. And therefore I can’t quite see what is the tension, what is the conflict between your project and just the general project of medical science.
Aubrey de Grey
Yes, very good question. The tension is there on many levels actually. First of all, of course, it’s there on the psychological level. We have this very deep-seated, long-standing belief that aging is inevitable and anything that tries to challenge that is viewed as suspicious. But also there’s a problem at the technical level as well. In general, when you want to cure a disease, eventually you may be able to come up with something that’s a real cure, like a vaccine for polio or whatever. But in the case of these age-related problems, the conventional approaches to them have really been ways to postpone them. Generally to postpone them not very much at all, because even if you can only postpone something by maybe 10, 20 years, that’s pretty good. That’s pretty much equivalent to something else. Because something else will kill you first. And that’s how these calculations are done when you ask people what they expect the effects of their up-and-coming therapies are. But of course it never happens that way, because progress does happen on all the others as well. So life gets longer and we carry on dying of the same things, in the same proportion as we used to. So the tension there is really that if you want something that gives you, let’s say, 50 years’ protection from a particular problem, then it’s probably going to be harder to develop and more expensive to develop and so on than something that only gives you 10 years’ help. So while you’re still looking at a 10-year thing as being quite attractive, it begins to be difficult to make an argument about the more ambitious approach.
David Deutsch
Are you saying that the 10-year thing isn’t particularly the best way to approach the 50-year thing?
Aubrey de Grey
Precisely. You’re absolutely right. Most medical technologies, especially these ones that are more or less explicitly admitting that they’re only postponement by a modest period, are not inherently extensible by an iteration of minor refinements. You have to really start with something.
David Deutsch
That’s very interesting. You mentioned philosophical issues. I’ve heard of the fact that in our culture death is supposed to be a great taboo. I haven’t actually heard of life being a great taboo. Yet it seems that the idea of science providing human beings with more life somehow causes the same kind of hostility as a taboo.
Aubrey de Grey
It is a taboo.
David Deutsch
So what is so scary about life?
Aubrey de Grey
It is completely irrational, there’s no question about that, except insofar as it can be regarded as rational from a psychological point of view. If we accept for the moment, which of course we don’t, that aging really is inevitable and nothing can ever be done about it, and if we also accept that aging is ghastly, then really we have to find some way of putting it out of our minds so that we can get on with our lives and not be miserable all the time about it. One way to do that is to come up with reasons to think that curing aging would be bad, or that aging is good, or at least that it’s six of one and half a dozen of the other. And it doesn’t really matter how irrational the reasoning is that leads us to that conclusion. It’s actually sort of worse than that, it’s sort of an inversion of the psychological problems, because as with anything, the more irrational your argument for something may actually be, the more you sort of know it’s irrational, and the more defensive, or perhaps even aggressive, you can become in maintaining your position against yourself and against others. You have to sort of hold it in place, you need more emotion to hold it in place, the worse it is as an argument.
David Deutsch
But what you call irrationality, this isn’t just a matter of really just people thinking that we owe our death to God or something, this is a general feature in our culture, religious, non-religious…
Aubrey de Grey
Absolutely, I think the major religions could be regarded as major examples of this, but that’s not the only example. My conclusions, if they’re correct, are extremely disruptive for society and so on, and so that’s something that politicians don’t tend to like, and therefore it’s not something that will endear gerontology to politicians, and so people worry about whether I may be hurting gerontology by scaring people and perhaps inviting a diminution of future funding. There is, however, also a scientific point that most of my colleagues genuinely disagree with me. However, it’s not really scientific, because the reason they disagree with me is largely because they don’t know what I’m saying, and so working scientists themselves, they appreciate that nobody has enough time to read what they’d like, and that’s certainly true for experimental biologists. And so of course it’s a bit of a Catch-22: you have to be persuaded that something is worth studying in detail before you study it in detail, and if you have to study it in detail in order to establish that it was worth studying, then it never happens.
David Deutsch
But you did say that your gerontology colleagues are… OK, well, let’s suppose that you’re right. This is science, we can’t guarantee anything. So we don’t know that these problems will be solved in time to save me or you, or we don’t know for sure that anyone alive today can be saved by this proposed technology, even though I’m actually quite sure for quite fundamental reasons that in principle it must be possible. That being so, though, isn’t there a danger when you’re promoting and arguing for this research philosophy, isn’t there a danger of raising false hopes in people?
Aubrey de Grey
There certainly is, and this is a very important question. The only reason I think that it’s legitimate to talk about timeframes, and of course the probability of those timeframes, as I always do, is because the opposite is also true. If one stays silent on something where the public have a predisposition, a very deep, deep predisposition in fact, to be fatalists and to think that nothing’s ever going to happen, if one stays silent then why engender an unwarranted pessimism? And of course the more pessimism exists in society, the more fatalism, the less people will agitate to get the work done and to have money spent, public money and so on, to get the work done, and that will delay the eventual development of this therapy, which will of course mean that lives are lost. So I feel that we have to press as hard as we can for this work to be done, and that entails getting people’s imagination up and getting their motivation up, and that entails talking about timeframes.
David Deutsch
Very good point. Well perhaps we can be doing this right now. Yes. There’s a whole other approach that I’ve heard of to what you might call the problem of immortality, namely what’s called cryonics, that is to freeze people just after they’ve died or notionally died, and in the hope that future technology will be able to both cure whatever they died of and also undo the damage done by freezing. Now that’s a completely different approach to yours. What do you think of it?
Aubrey de Grey
Well actually I think it’s quite realistic, and the reason I think it’s realistic is because you’re wrong. It’s not a completely different approach at all. It’s merely a sort of add-on to my approach. My approach is to take people who have not yet died and repair the damage that has accumulated in them as intrinsic side effects of metabolism throughout their lives, and thereby maintain them in a youthful condition both physically and mentally. Now when you die officially, in other words when you become legally dead, not much has happened. Basically the difference between being legally alive and legally dead, or clinically alive and clinically dead, is not in the state you’re in, but in the rate at which that state is changing. So you’re gradually going downhill, then your heart stops, and you start going downhill a lot faster, but that’s still fairly slow. And that’s why cryonics is reasonable. It means that if one can be cryopreserved, taken down to liquid nitrogen temperatures or thereabouts, within a small amount of time, a matter of hours ideally, from the point at which one’s heart stops, then the amount of damage that has occurred in the process of post-death decay is relatively minor. So that means that you preserve a person in more or less the same state that they were in just before their heart stops. Now as you said, damage may be done during the cryopreservation process, though in fact that problem is more or less history. There are now cryoprotectants that are so good that no crystallization at all occurs in the process of taking someone down to liquid nitrogen temperatures, though there are still problems with crystallization during the warm-up process and there are one or two other problems with fracturing and so on. But anyway, progress has been made very rapidly. There is a toxicity problem, a chemical toxicity problem with these cryoprotectants, but again, progress has been made there. So really, as far as I’m concerned, the main challenge to resuscitating someone who has been cryopreserved in the best possible state that we today can manage is actually to solve the repair of the things that accumulated before they died, which is exactly what I’m already working on. That’s why I say that cryopreserving is just an add-on to what I’m doing already. You see, because the first generation of these technologies, when we develop them, probably if you were at death’s door, we won’t be able to help you very much, because they will be very elaborate and exploratory technologies that will be quite tenuous and you probably won’t be vigorous enough to withstand them. But as time goes on, rather rapidly after that, these technologies will be improved in not only their convenience and cost and comprehensiveness, but also in terms of those characteristics that make them effective in people who are nearly dead. And therefore, we’ll be able to pull you back progressively closer and closer to the brink. And of course, as I said, there’s not really a brink at the point your heart stops. So in other words, it seems perfectly reasonable to suppose that incremental improvements on those same technologies will be able to bring you back from a little way beyond the legal brink.
David Deutsch
That’s all very optimistic and good. Now, again, supposing that you’re right, if somebody were to walk in here now with a gun and say, you know, I’ll kill you in five minutes or I’ll kill you in a year or whatever, unless you do so-and-so, unless you hand over this priceless dinosaur or unless you give me all your money, I think most people would be inclined to say, well, life is more important than just property. So, you know, they’d be inclined to give at gunpoint whatever is asked more or less. They’d be willing to give quite a lot before they begin to think it’s not worth the candle. As we’ve discussed, though, somehow in regard to natural aging, people take the opposite view. They would rather die than hand over material goods in the form of research funds for you. But nevertheless, they do have a germ of a point there, which it seems to me is this. What proportion of our national wealth or the wealth of the world should, and also intellectual effort and also dislocation from social change and so on, what total effort, what total proportion of our effort do you think it is rational for the world to give your project?
Aubrey de Grey
I really don’t know, and the only reason I’m content not to know is that I see the process evolving through a period, the first period in which there is only a very small amount of money being spent by medical research standards. And at the end of that period, there will be interim results in the laboratory in mice that will convince, first of all, gerontologists as a whole, and thereby society as a whole, that this is possible. At the moment, there is, as we’ve discussed, a general feeling that this whole thing just can’t be done, that aging is inevitable. And that will be overthrown by results in the laboratory, which are relatively cheap. Now that means that once those results have occurred, there will be a great debate in society with regard to exactly the question you’ve asked, among others, about how much we ought to throw at this, whether and how much we ought to throw in fact at other things that we throw a little at the moment, like for example the development of vaccines or giving people in Africa mosquito nets and whatever. I think all of these…
David Deutsch
Yes, because this is worth doing, and a whole load of other things are also worth doing.
Aubrey de Grey
That’s right. Our whole system of priorities in terms of spending will have to be completely rethought, and I suspect that that rethinking will be energetically pursued as soon as the progress in the laboratory is sufficient to persuade gerontologists as a whole, rather than just me.
David Deutsch
That’s very reassuring. It’s very nice to see that you’re optimistic, not only about your scientific research, but also about the prospects of persuading the world at large that it is worth it.
Aubrey de Grey
I’m optimistic, but I think we ought to be careful about how we use the word optimistic, because as you were saying earlier in your upcoming book, you’ve discussed this a bit, but in a sense there’s a certain suspicion about optimism in modern society, and the word optimism has this sort of double-edged ring to it, as if it’s optimistic, almost synonymous with over-optimistic. So I think I want to make the point that I’ve thought about these things pretty hard, and I reckon that my conclusions are accurate, as accurate as they can be, neither optimistic nor pessimistic. I think that the reason why society will follow the opinions of the gerontology consensus is borne out by the fact that general belief in society in scientific matters follows the consensus of the relevant scientific community in pretty much everything else, so we have a great deal of precedent from which to make that conclusion. Similarly, I think based on my knowledge of the field in gerontology, I know what it’s going to take to persuade my colleagues not just to believe that we are within striking distance of seriously postponing human aging, but actually to say so on the television. And so I think both of those things are going to happen when we get a particular milestone, as I always talk about with mice.
David Deutsch
Well, that’s wonderful.
Aubrey de Grey
The hardest one is WILT and cancer, and that’s going to involve quite sophisticated stem cell therapy, but it’s also going to involve quite sophisticated gene therapy. And gene therapy, of course, is important in a bunch of things. It’s important for getting the bacterial genes into our cells once we’ve found the genes, and also it’s important for putting the mitochondrial genes into the nucleus, because we have to do modifications in the laboratory and test it before we can do that. Gene therapy is an area which, again, people are being very illogical about. In terms of proof of principle, I’m particularly aware of it, and it’s what I’m really interested in right now. Gene therapy is really going quite well.
David Deutsch
In all these cases, in all seven of these lines of research, can we think about translating from the scientific breakthrough to the therapy, to what it will look like from the punter’s point of view? How can I visualize this? If this worked, would I be, let’s say, visiting the doctors every Christmas and getting an injection of something which will rejuvenate me? Or will it be really serious, aggressive intervention that will take up 90% of my time and I’ll spend the rest of the time enjoying it? Or what?
Aubrey de Grey
I think that at first, when the first therapies arrive, they’re bound to be quite strenuous, quite experimental, quite elaborate. I wouldn’t be surprised if it would entail going into hospital for a month and having all manner of different stem cell therapies, for example, some stem cells injected into the bloodstream, others injected into the brain, maybe directly or into other tissues. Gene therapy, again, by injections, probably using viruses, which are the main ways in which we do gene therapy at the moment. It’ll also involve vaccines, it’ll involve standard drugs as well.
David Deutsch
So it won’t be very nice to have this done to you?
Aubrey de Grey
Well, at first it’ll be a month in hospital, and then you’ve got 10 years before you have to come back. And the point is that in those 10 years, of course, there will have been a lot of pressure, a lot of market pressure, to improve these therapies, so that it takes place quicker. And I wouldn’t be so surprised if 10 years later it takes a day in hospital. And it wouldn’t surprise me if 10 years after that one doesn’t need to go to hospital at all. One just goes to one’s GP and has a bunch of injections. I put probabilities on this, not just to say this will happen in this particular period of time, but to say I think that we have this amount of chance of this happening in this period of time. However, I do like to stick my neck out and give such timescales. Most of my colleagues refuse to do so, they say it’s engendering unwarranted optimism in society, to put timescales on things that we don’t know. I say that’s nonsense, I say we’re engendering unwarranted pessimism if we stay silent. So my timeframes are, I think, that with sufficient funding we should be able to reach the first milestone that I like to talk about, which is real serious life extension in mice within 10 years. Now when I say serious funding, I mean something in the region of $100 million a year over 10 years. Not even by scientific research standards, certainly not by military standards. What I mean by serious life extension is two things. First of all I mean that the actual length of life has to be improved, and in particular it has to be healthy life that’s improved. I’m not talking here about extending people or mice’s frail life. But secondly, and very importantly, the therapies have to begin when the mice are already in middle age. And also the mice have to be pretty healthy, robust, long-lived mice naturally. So what that means in round numbers is that we take a strain of mice that would normally live about three years, that’s on the high side for mice. And we do nothing at all to them until they’re already two, so they’ve got a year left, and we can treble that, we get them to see their fifth birthday on average. If we can do that, we’ve trebled the remaining lifespan of healthy mice, starting from the point where we started therapy, then I think that will convince all my colleagues that we’re on the right track, and that it can be done in humans as well.
David Deutsch
That’s amazing. Like one of my earlier questions, where the existing medical research fits into this scheme? One of the things that has to be done is basically curing cancer. Curing cancer is already something that there’s a lot of money going into and so on. So are you saying that you’re going to ride the wave of the cancer cure that is coming anyway, or is this project going to somehow accelerate even cancer cures? If so, why is it not already mainstream?
Aubrey de Grey
Right, the reason is, essentially, it’s a fine example of what I was saying earlier about modestly effective therapies that seem to be relatively easy to develop, being preferred over extremely ambitious therapies that might be much more effective. So I’m looking at developing therapies that could give us a postponement of death from cancer by maybe 50 years, at least. And nobody else is looking at therapies that would be able to do that much. Basically, the power of natural selection in cancer is sufficient that any therapy which can, in principle, be escaped by the cancer, if the cancer can just turn on or off the right, appropriate constellation of genes, will naturally be escaped by the cancer. I think that the milestone that I’m interested in for humans is a little bit less extreme in numerical terms than the milestone of mice. The mice, as I said, take about two thirds of the way through its lifespan and treble its remaining lifespan. For humans, I think it would be good enough to double the remaining lifespan. So in other words, take someone who’s maybe 55, got 30 years left on average, give them the next 30 years in good health, of course. Now the reason that I’m aiming for this rather less ambitious goal…
David Deutsch
You’re aiming for what, 150?
Aubrey de Grey
150, that’s right. Now the reason I’m aiming for this rather less ambitious goal in quantitative terms is because 30 years is such a long time in science. In 30 years, as we’ve seen in all these other technologies, if one has the public motivation and also if the advances that need to be made can be made incrementally in relatively small steps, in 30 years one can basically completely transform a technology just by progressive refinement to something that’s much more effective than it was originally. So I’m very confident that if we can develop therapies which can give 55-year-olds an extra 30 years of life, then by the time they get to be biologically 55 again, when they’re, let’s say, 85 or 90, the therapies that have been developed in the meantime will be so much better than the ones they got when they were 55 that they won’t just have another 30 years left. They will get these new therapies and have another maybe 50 more years left, or 100 years. So basically this means that it’s a bit like keeping a vintage car going. Vintage cars don’t have a mortality rate. They only die when they’re not maintained well enough to keep going pretty much indefinitely. We just have to develop the same degree of technology for humans and we’ll be done. And I’ve been calling this concept life extension escape velocity because what it means effectively is that technology is improving faster than the remaining imperfections in the technology are catching up with us. And therefore the amount of microscopic damage, molecular and cellular damage, which is in the body at any one time, is not ever able to rise to a level of abundance that’s actually causing loss of function and disease. Of course what that means for life span is that people have done this calculation a few times over the years and people get slightly different answers. But to within a factor of two people reckon that we would live to about a thousand if we didn’t have any aging at all. And that’s based on how often we die. People in the West, people in wealthy societies in the West, die of causes that have nothing to do with aging, whether it be crossing the road carelessly or homicide or infectious diseases or whatever. Now interestingly of course that calculation is a bit naive because…
David Deutsch
As we can affect the risks.
Aubrey de Grey
But realistically we are likely to reduce that risk. I think we’re likely to become considerably more risk averse in consequence of knowing that we have so much more at stake. When I was writing a book about 20 years ago on the science of some of these things, I had a few pages at the end about the social context and one thing I predicted then was driving would be outlawed. And I think that may be an overstatement. I think that simply what may happen is we’ll throw a lot of money into the problem and we’ll all drive incredibly safe cars with very sophisticated sensors that can avoid serious injury even in the context of really massive human error, whether it be by the driver or by the pedestrian.
David Deutsch
Our risk aversion seems to be increasing anyway even without that extension.
Aubrey de Grey
I think that’s absolutely right. I think it’s not just our risk aversion either, it’s our…
David Deutsch
Impression of the value of life. We value life more.
Aubrey de Grey
Impression of the value of life, that’s right. I think the fact that we’ve abolished, of course, the death penalty in all of Europe since the war, with the exception of course of countries like the former Soviet Union, I think this bodes well. And of course the same can be said of other aspects of society. The fact that for example in the West, the birth rate is declining so rapidly, this means that we may have longer than we might otherwise think to be able to cope with any overpopulation problems that might arise from essentially eliminating death from aging. So yeah, these are reasons for optimism being realistic.
David Deutsch
Thank you.
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