A Precursor to Cryonic Revival
Posted by Jeriaska on September 1st, 2007
Aubrey de Grey presenting at the 6th Alcor Conference in Scottsdale
Aubrey de Grey is the editor of Rejuvenation Research, the world’s only peer-reviewed journal focused on intervention in aging, he is an advocate of research seeking answers to how molecular and cellular metabolic damage brings about aging and ways humans can intervene to repair and/or obviate that damage. At the 2006 Alcor conference in Scottsdale, Arizona, he gave a presentation on how implementing Strategies for Engineered Negligible Senescence might be viewed as a precursor to the prospect of reviving patients from cryonic suspension.
The following transcript of the 2006 Alcor conference presentation by Aubrey de Grey has been corrected by the author and approved for publication. DVDs of the 6th Alcor conference are available for purchase at the Alcor website.
“If SENS is something that I can go head-to-head with skeptical gerontologists about and usually win, which as you may know I have been doing lately, then we are only two steps by alternative paths from achieving the same sort of credibility for cryonics.”
SENS: A Precursor to Cryonic Revival
I’m going to first of all conduct what I can best describe as a brief ceremony and I’m not going to tell you any more because I think you’ll find out what I’m talking about in a few seconds. Then I’m going to spend probably the first half of the talk talking about my own views of how we might seriously postpone and indeed defeat aging without the help of nanorobots. I’m then going to talk in terms of, I guess, public relations, and where I see the opportunity increasingly arising to be able to make a better case for the feasibility of cryonic revival than we have historically been able to make. And I will also touch briefly towards the end of the talk on what I see as the really rather strong likelihood of a very sharp increase in the take-up of cryonics that might happen really quite soon without something so dramatic as a rat being cryopreserved and then revived, for example.
The Methuselah Mouse Prize, which we now simply call the Mprize, is doing quite well at the moment. This is the amount we have in the bank if we include pledges made by what we call the 300 Club: people who have undertaken to give roughly $1000 a year for 25 years. And we’re pretty happy about all that. It’s been growing as fast as any of us could have hoped it would during the four years that it’s gone forward so far since David Gobel and I founded it. One thing that has also happened during that time is that the number of individual donors has been going up at a nice respectable rate, and that’s very important, because after all the Mprize is really part of our campaign to popularize life extension. The number of official donors came up to 400 just yesterday, if I’m not mistaken. But actually that number is not precisely accurate, and here’s why. This is one of the entries in the list of donors. The donor’s name is Avianna Vyff. It says here when the donation was made and the amount, which is $3002. The way that Avianna raised this $3002 is also mentioned here. She decided to canvass the grown-ups in her neighborhood to donate to the cause. And the number of donors that Avianna succeeded in attracting donations from was really rather large. So, we thought that it would be important to demonstrate our appreciation of this. I made a little certificate here, which I’d like Avianna to come up now and receive this, if you would.
Avianna: I was just going to say why I did this, and mostly it’s because I thought at the time, and I still do, that if people could live longer then we could help with a lot more problems around the world, like poverty and sickness, and we also might be able to make it off the planet soon. But mainly it’s to help lots of people who I know, and some who I don’t know, that are suffering from aging and other diseases.
Thank you very much. Another round of applause for Avianna.
That’s all I am going to say about the Methuselah Mouse Prize today. I’m going to focus mainly on the other activity of the foundation, and I’m just going to spend a couple of slides now explaining why the Methuselah Foundation has both of these activities. The record of prizes over the past few centuries in spurring innovation is very impressive indeed. Many of you have probably heard of the Longitude Prize, which was offered for a time-keeping device sufficiently accurate to be able to allow ships to know where they were when they were crossing oceans. The Orteig Prize was offered for the first flight across the Atlantic and was won, of course, famously by Charles Lindbergh. And more recently the XPrize for space tourism. Many more of these exist, and the key point is this: that it’s a very efficient way to get money spent on important technological innovations that catches people’s imagination. Exactly what proportion it is depends on what numbers you look at, but in some cases it’s at least 1/5th, while in some cases it is closer to 1/50th of the money that is spent has to be in the prize kitty in order to make the whole thing work.
So the question is when are prizes appropriate? And this is how I think about it. Prizes are really good when nobody really knows what is going to work. Nobody knows where to start but lots of people have their own ideas. It is not so appropriate when the consensus really is pretty confident about what’s going to work, and the question is simply resources. The classic case given here is either the Apollo Project or the Manhattan Project. I don’t think it would have been quite so appropriate to encourage those sort of things to work simply by offering a prize incentive.
So another question is, What is the situation with life extension? The position that we in the Methuselah Foundation have is that it’s hard to say, because we have a detailed plan for how to fix aging, but we don’t know whether my plan is going to work. So we would like other people to have a go as well. And therefore it makes sense to hedge our bets by promoting both the organized approach and the distributed approach.
I’m going to move onto what SENS is, and a little bit about the science of it. And in order to present this, I really have to start by defining what the problem of aging is. Aging is a side effect of being alive in the first place. In other words, it’s the accumulation of damage. And one of the most important things that I always have to get across to any audience, and especially audiences who are not all expert biologists, is that one has to demystify aging. One has to explain what aging is in a manner that gets people out of the mode that it’s something that we can’t fix, because it’s something that we don’t understand. The fact is that we do understand aging. Aging is simply a maintenance problem. It’s the accumulation of molecular and cellular damage. This damage accumulates as a side effect of normal metabolic processes, and therefore it accumulates throughout life. And eventually it causes pathology. It causes bad things, whether they be age-related diseases or frailty and general debilitation that we don’t necessarily call diseases.
Here is a big problem: this is metabolism. Metabolism is unbelievably complicated. In fact, it’s much worse than this, because this is simply a summary of some subset of metabolism that we actually understand already. And the amount that we understand is a tiny fraction of what’s really going on. You won’t find any biologist who would dispute this. It’s absolutely clear that we have hardly scratched the surface of the complexity of even how cells work, let alone how organisms work.
So, stopping it from laying down all this damage seems like a tall order. Here’s a second problem. The pathologies are extraordinarily many and varied as well. This is a small list of some few of the ‘thousand slings and arrows that flesh is heir to,’ as Shakespeare said, and it’s hard to know how to keep all of these things at bay. This is really the conclusion that people in the field have come to over the decades that they’ve been worrying about this. That neither of the two obvious ways of going about postponing aging is really particularly promising at this time. I’m calling them here the gerontology approach and the geriatrics approach. The difference between them is how far along the chain of events from metabolism to pathology they intervene.
The problem with the gerontological approach is that its heart is in the right place, so to speak, with the idea that prevention is better than cure, but we understand metabolism so poorly that it’s more or less impossible to improve on metabolism and clean it up, and to do better than evolution has already done. Conversely the geriatrician’s approach has the advantage that intervening in the pathology directly does not require understanding how the pathology arose in the first place. But, on the other hand, because things have spun out of control at that point, it’s a losing battle.
So, the conclusion that all of my colleagues have come to is that aging will continue to defeat us for centuries. And the reason I don’t agree is the fact that things only start going seriously wrong in the body during the second half of life is a big opportunity. Because, as I mentioned earlier, aging is a side effect of metabolism and therefore the damage that is the precursor of pathology is accumulating throughout life. By definition, more or less, metabolic consequences happen throughout life, because metabolism is a set of chemical reactions. So there must be some sort of threshold level below which these side effects, this damage, is inert and harmless. So, we can say this: Yes, damage eventually causes pathology, but metabolism ongoingly causes damage. Damage is being defined, for the purpose of this talk, as the intermediary between metabolism and pathology that are only present at the molecular and cellular level. They are not actually causing functional deficit until they get up to a level of sufficient abundance that metabolism can no longer function in their presence so well as it used to.
The reason this is so useful is because it gives us a third way of intervening in aging other than these two. We can put damage in my diagram down here and we can say basically gerontology is about slowing down the rate at which metabolism causes damage, and geriatrics is about slowing down the rate at which damage causes pathology, and the third approach, which I like to call the “engineering approach,” says, Let’s not do either of those things. Let’s actually intervene at an intermediate point in the chain of events. The logic here is that we get the best of both worlds. We get the best of the geriatrician’s world in that we don’t have to understand what’s going on up here very much in order to intervene in this initially inert family of changes that accumulate in the body and that I’m calling damage. But at the same time, we’re intervening early enough in the chain of events that things have not yet spiraled out of control, and we have the chance of being able to do this indefinitely.
I claim that this adds up to being a good reason to suppose that the engineering approach can achieve substantial, and in fact dramatic extension of human lifespan, and healthy lifespan, relatively soon: on a time frame of decades. I like to use the analogy of houses. I think I might have used this four years ago. Houses are a success story of civilization. We have houses, in my country anyway, that have been up and continuously working as habitable places for hundreds of years. Now, they weren’t built to last hundreds of years, most of them. They were built to last maybe fifty years. And the reason why they have lasted longer is because we now know how to make them last longer. We know how to do the maintenance.
Here’s one thing that happens to a house with no maintenance: storm damage happens in the roof and water gets in. You get pathology: staircases collapsing and ceilings falling down, and so on. So our three heroes from the previous slide are up here. You have your geriatrician running around worrying about the pathology: putting the up the ceiling and the stairs but not worrying about the initial damage, and it’s a losing battle, obviously. The owner is going to have to find somewhere new to live fairly soon because water is increasingly accumulating in the fabric of the house. The gerontologist is trying to be preemptive and plant tall trees around the house to diminish the rate at which storm damage would happen in the first place, and that’s problematic, because he’s introducing a new problem: namely, the possibility that the storm will blow some big branch off the tree that will smack into the roof and make a bigger hole than would have happened anyway. The gerontologist in this allegory doesn’t understand the weather. He only understands the damage. And so he’s making a mistake, that’s making matters worse. Whereas the engineer is intervening at the appropriate point in this chain of events, so to speak, by fixing the damage as it accumulates.
Now the question of course is why is this analogy something that I think is valid. And the answer of course is: because the damage is much simpler than either metabolism or pathology. I have been making the somewhat outrageous claim over the past few years that all the types of damage that really matter, that significantly contribute to age-related illness and functional decline can be fitted into these seven major categories: intracellular molecular garbage, extracellular garbage, depletion of cells (cells dying and not being replaced), cells accumulating and not dying when we would like them to, mutations in the chromosomes and in the mitochondria, and stiffening of long-lived tissues due to new chemical linkages that accumulate in them.
No new type of damage in addition to these seven categories has been identified for 24 years now. That’s pretty good news. So we can look at it like this, here are the types of metabolism and pathology in 2 point font, but you just have this small number of damage types that intermediate between the two. If we could deal with all these, if we could fix them all, then we would be uncoupling metabolism from pathology, and we would have solved the aging problem.
So the question is, How close are we to fixing these things? And before I show you the next slide, I want to emphasize that when I say “fix” I don’t mean “stop the damage from happening.” I mean fixing the damage itself after it has happened. It’s central to my whole thesis that what we should actually be looking at is not taking the concept of prevention being better than cure too far. We should be actually looking at repair and maintenance processes, which may be easier to implement than preemption processes. And the short answer is, I think we know how to fix them all. We can’t do it yet, but I’ve developed this panel of proposed interventions which I call SENS, which stands for Strategies for Engineered Negligible Senescence.
Here they are. You have all heard of stem cell therapies. This is how we will fix the problem of cell death without compensatory replacement of cells happening naturally. We fix that through artificial medical replacement of those cells. And you can go down the list. The bottom three are the hardest ones, and they are the ones that I have been working on myself. The other ones are actually going pretty well. Most of them are already in clinical trials already. The hardest ones are only about ten years away in mice, and perhaps only another 20 years away in humans, though that’s much more speculative.
Here’s my mouse milestone. And the reason I think it’s only ten years is because of the amount of detail that we have already in exactly how we would go about implementing these fixes to the various types of problems. This is my definition of a milestone that I think will change public attitudes to life extension irretrievably. Most mice live about two years. Really nice long-lived strains of mice that are already pretty healthy live about three years. What I’d like to do is take mice of such healthy strains and wait and do nothing at all to them until they are already two years-old, already in middle age. So, they have a year left. Up until that time they have had nothing genetic done to them, nothing dietary, no drugs. To treble their remaining lifespan is what I want to do.
That is a pretty tall order. But I don’t think it’s impossible. In fact, I think it can be done with sufficient funding. We would need quite a lot of funding: $100 million, for ten years. And I think if we had that, we’d have a 90% chance of success. Because all of the various approaches to fixing these seven problems that I think have a good chance of working could actually be supported. We’re talking of something in the region of 500 full-time scientists, with all facilities and equipment. It sounds like a lot of money, but it’s more money to some people than it is to others. A couple weeks ago, as some of you probably know, we made a good start. Peter Thiel, who co-founded PayPal, and who became really rather wealthy a couple of years ago, having been the CEO of PayPal when the company was sold to eBay, is slightly less wealthy now that he has given three and a half million dollars to me, and he has done so in order to accelerate this work.
This means, from my point of view, that we are a big step forward to getting the $100 million a year that I need to fix aging in mice in ten years. So, that’s what I’d like to do. In terms of how long it’s going to take to get things working in humans, it could be another 15 or 20 years after we get mice working. I think we’ve probably got a 50% chance of that being the case. But it could be 100 years if we get unlucky with the science. A 50/ 50 chance is worth trying. Now, I’m going to talk a little bit about PR. Cryonics, of course, has been around a lot longer than SENS has. And cryonics still only has 1500 or so people signed up as members. This is a problem that you guys have been addressing with a great deal of expertise and creativity for a long time. But the fact is, we haven’t cracked it yet. We haven’t sold cryonics to the masses.
Cryonics is not a disposal of human remains but a rather a type of critical care. We all appreciate that this is a great tragedy, that people are passing up the chance of a longer life. There are many reasons why so few people sign up. I’m not going to bother to enumerate those reasons because most of you here are familiar with the field and what these reasons are. I’m just going to talk specifically about one of those reasons, which is skepticism as to whether the technical ability to revive people, and of course to fix the problems that they died of in the first place, will ever be developed.
Now, I think a lot of us, especially those of us with a scientific background, understand that the whole point of cryonics is that we have as long as we want for humanity to develop the technology. And therefore, the problem can be pretty much arbitrarily hard, because we will get there eventually. Liquid nitrogen temperatures are low enough that that’s okay. But it just doesn’t seem to get through to most people. Most people just don’t like the nanobot argument. The fact that we don’t need to know yet how to revive patients is just not very helpful rhetorically for most people in my experience. They don’t deny it. They just find it fishy.
I was particularly motivated to talk about that today when I watched Death in the Deep Freeze, and Arthur Rowe, a senior member of the cryobiology community, and vocal skeptic with regard to cryonics, was interviewed extensively. This is one thing that Arthur Rowe said in that film. “Do I think that the money spent on cryonics is a waste? By and large, yes. Those people who are working on trying to preserve organs, it’s an admirable thing. But cryonics has no redeeming value.” Now, hang on. What is so different from a cryobiology point-of-view? Let’s leave all of the ethics and all of the philosophy out of it. Because this guy, Arthur Rowe, he’s a cryobiologist, right? Now, correct me if I’m wrong, but I thought the brain was made out of cells, same as the rest of us. How can the brain be considered to be so different from the liver or the kidney or whatever, that it’s “admirable” to make cryopreservation work for organs, but cryonics itself has no redeeming value?
It really struck me that it was something that someone should have actually challenged Arthur Rowe on film to see what he could say. So, I’m going to leave that with you for a second. I work not in cryonics but in trying to avoid cryonics. We all know that cryopreservation is the second worse thing that can happen to you. I imagine Ralph was the first person to say that. He was the first person to say most of the clever things in this field. One thing that I often get asked is, What is the point of being physically young if you can’t keep the brain going. And of course that’s not true. The brain is made of the same stuff. The molecular and cellular therapies that I’m interesting in getting developed are no different in the brain than other tissues.
Perhaps you could say that we have less certainty that they will restore and maintain function in the brain than we have for other tissues, because we understand so much less about how the brain works in detail. We don’t really know that the brain will carry on being able to work as flexibly as it does when we are young. In other words, when we are in our first hundred years of life. But it remains to be seen. The therapies certainly have a good chance of working. So, I’m going to bring those two things together now.
It seems to me that the technical feasibility of cryonics is hard to sell, because real people out there don’t like arguments along the lines of “It doesn’t matter how hard it is, because we’ve got arbitrarily long.” They don’t like arguments that involve infinity. They just sound fishy to most people. Not for any good reason, you understand. Arguments involving small numbers like “2+2=4″ are altogether more effective it seems. This is what it really comes down to. Ultimately we are talking about four different concepts here: rejuvenating the body, rejuvenating the brain, reviving the body from cryostasis, and reviving the brain from cryostasis.
If rejuvenating the brain isn’t much harder than rejuvenating the body, then that probably means that we can get from reviving the body from cryostasis to reviving the brain from cryostasis. The difference in difficulty there will be similar. If we can get from rejuvenation, the sort of thing that I work on, keeping people’s organs going by maintenance when they’re still functioning, to reviving those organs from cryostasis, if that’s not a terribly big leap, then perhaps it can be done for the brain. So what that means is that if the type of medical research I work on is legitimate, then that’s a good start. Similarly, if cryobiology is a legitimate, even admirable field, including cryopreservation and resuscitation of organs, then we shouldn’t really have too much difficulty in believing that cryonics is technically feasible in the foreseeable future.
I find that this argument works rather well. And I have plenty of time for Rob Freitas and Ralph Merkle’s work on nanorobots. I think that it is more or less certain that we will need nanotechnology and artificial intelligence to revive James Bedford, or indeed anyone who was cryopreserved more than about ten or twenty years ago. But I think we have now reached, with the development of M22 and other important developments, the point where it is reasonable to argue from a prfoessional biological perspective that we may not need that for people who are cryopreserved with the best state-of-the-art technology available today.
Now, of course, twenty years ago you could have said to someone who was skeptical about the technical feasibility of cryonics, ‘Now, hang on, you’re probably not going to die in the next twenty years. There are twenty more years of technical progress that you will be able to take advantage of before this matters. Therefore, you shouldn’t worry about how things look now.’ But that’s the same sort of argument from infinity that people don’t seem to like. We don’t need that anymore. Now, we can argue from what we know. If SENS is something that I can go head-to-head with skeptical gerontologists about and usually win, which as you may know I have been doing lately, then we are only two steps by alternative paths from achieving the same sort of credibility for cryonics.
You may remember that I defined the concept of robust mouse rejuvenation earlier. I want to talk a little about the impact of that on cryonics. It strikes me as pretty certain that rats will not get up from a cryopreserved state with no warning. In other words, the people who are working on the cryopreservation of organs interact a lot with the cryonics movement. The rate of progress and the plausibility of that sort of event, there will be some warning. But that’s not the only development that in my mind could cause a really dramatic acceleration in the interest in cryonics. As I mentioned earlier, there are many reasons why people don’t sign up for cryonics, but the technical feasibility as people see it is a big one.
The argument for nanobot-free feasibility for this in the long-term is a good start, but ultimately things may happen fairly soon that are not actually directly relevant to cryopreservation , but which since cryonic resuscitation is ultimately a natural extension of resuscitation, repair, and maintenance of people who are still alive in the legal sense, that extrapolation is going to be made by the general public when dramatic things happen in the laboratory in life extension.
Here is what I think might happen in ten years time. Middle-aged mice being rejuvenated in a very dramatic manner, so their remaining lifespan is trebled. The reason it is going to be dramatic in sociological terms is not because people will pick up their papers and read about it. It’s because people will pick up their papers and read about the opinion of the gerontological consensus concerning what it means for the prospects and the timeframe for the corresponding results in humans. Gerontologists, and I can tell you because I know them all personally, when these mice get up and walk around for two years longer than they were otherwise going to, my colleagues will not hesitate to say, Yes, we don’t know how long it’s going to be, but it’s only a matter of time before we seriously fix aging by the same sort of means in humans.
Another thing that may have happened by then is that in the case of organs other than the brain, cryostasis may very well have been validated considerably better than it has so far. The logic that I gave you earlier, that 2+2=4, is going to be rather hard to escape. People are going to put 2 and 2 together and realize that if revival from cryostasis is a natural extension of repair of legally living organisms, and if also we have your middle-aged mice being rejuvenated and organs being restored to function, then it will be very difficult to argue that it’s essentially impossible that cryonics will never work. The critical thing I want to point out is that this will be the first time ever that one of the major reasons not to sign up for cryonics has ever been eliminated in the opinion of the general public. And this very well might happen quite soon.
So, it seems to me that we can’t simply say, Well, this is only one of the many reasons why people don’t sign up, so it might double the number who sign up, but it certainly won’t send it through the roof. I don’t really think we can say that. Maybe one way to anticipate the turbulence that lies ahead is to buy stock in something that cryonics needs. So, my conclusions are here. Reviving patients from cryostasis may be so hard that it needs nanotech and artificial intelligence. I think that’s certainly true for patients who were cryopreserved a long time ago. But for patients who were cryopreserved with the best technology available today, it may not take nanotech and artificial intelligence.
We already, when we talk to people about cryonics, appeal to the probabilistic logic. – “It’s certainly a lot better than being the controls.” So, finally, I think that from a PR perspective we might make some headway by stressing that the difference between cryonic resuscitation and the sort of medical advances that I work on as a biogerontologist is actually rather small. And that that is an easier argument to sell than an argument that’s based on infinity. So, I’ll stop there. Thank you.
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