February 03, 2020
Around the world, people are living longer — not just because child mortality is dropping, but also because we’re staying healthy for more years as we age. In the future, regenerative medicine and other new developments may help most people remain youthful much longer than they do today. In this talk, Aubrey de Grey, Chief Science Officer at the SENS Research Foundation, discusses the biology and sociology of what could be a massive shift in the way we live.
I am delighted to be here. This is the first time in five or six years that I have spoken at an EA [effective altruism] event, and I am very impressed by how rapidly and how far the EA movement has grown.
What I'm going to do today is try to explain why I believe it makes sense for effective altruists to prioritize the issue of aging. To make that case, there are a number of questions that need to be answered in the affirmative.
First, is aging a really big problem? I believe that it is, by a good distance, the world's biggest problem. But I understand that this group thinks very carefully about such statements, so I need to justify my opinion.
The second argument I need to make is that we have a sufficient understanding today of what aging is, and generally how we might go about addressing it. Therefore, if we throw money at this problem, there’s a good chance of having a significant impact. This is not trivial. Other times that I've spoken at EA events, I've received a lot of pushback. [Many EAs believe] we understand so little about aging that what we do [at the SENS Research Foundation] is essentially random, and therefore [spending money on it is unjustified].
The third argument I need to make is very new. It's really only arisen over the past few years, and it is this: Philanthropy [is still] critical, [even though] private investment [in the study of aging] has exploded.
To address the first point — why aging is important — I'm just going to tell you why I think that is clearly true. To me, it’s just a fact that aging causes far more suffering than anything else in the world today or in the foreseeable future. It's not just the death part. We're talking about effective altruism here, and altruism means worrying about other people. People dying makes other people unhappy. That's not arguable.
But what might be much more important is that when people die of aging, they do it slowly. They do it as a consequence of a chronic, progressive accumulation of damage in the body, a decline in mental and physical function. That's a lot of suffering, too — for the people who are actually aging and for the loved ones of the people who are aging. So, to me, it's [self-evident] that aging is, by far, the source of the largest amount of suffering in the world today. You could even argue that it was true a long time ago.
I also want to emphasize that this is not only about the industrialized world. Something that we often overlook is that the developing world is catching up in terms of longevity, and therefore, in terms of how much they experience the health problems of late life. In the World Health Organization’s most recent statistics, there wasn't a single country in the world with an average lifespan lower than 50. Outside of Sub-Saharan Africa, there wasn't a single country that had one lower than 60. So we can see that the issue of aging is not just a first-world problem. It is an absolutely fundamental problem for the entire world.
Now I'm going to address the second question of whether we actually understand aging well enough [to ensure that funding it will have] a significant impact. In order to do that, I'm going to fill in a lot of background information.
First, why is it that aging is a problem at all? Why has it resisted the medical advances that have been so successful against most infectious diseases?
Over the past 200 years, we've brought infant mortality down from something like 40% (which is where it was 200 years ago, even in the wealthiest countries in the world) to nearly zero. And we did it through ridiculously simple measures, like figuring out that hygiene is a good idea.
So, what is the problem? Most people would say it's that there's so much that goes wrong with us late in life — and it all goes wrong at the same time, so these things interact with one another.
It's the complexity. And that’s part of the answer. But it's by no means the whole answer.
In order to explain the whole answer, I need to define aging, which is crazy. How on earth could we not yet have a good understanding of the process that has preoccupied humanity since the dawn of civilization? But if you ask people what aging is, you will not get the same answer from everybody. I'm going to use a very simple definition.
Aging is the combination of two processes [metabolism and damage, which together result in pathology]. Metabolism goes on throughout life, starting before we're even born. A network of processes keeps us alive — that's what metabolism means — [and, over time,] generates damage.
“Damage” is the right word to be using for the various changes to the molecular and cellular structure of the body that are brought about by metabolism, because the body is only set up to tolerate a certain amount of change. After that, the body starts to function less well, both mentally and physically. And that, of course, [leads to] the late-life emergence and progression of the pathologies of aging.
Currently, the overwhelming majority of money and effort spent to prevent the pathologies of late life is spent wrongly. It is spent on trying to break the link between damage and pathology.
That is insanely stupid. Damage, by definition, is accumulating, which means that efforts to stop it from causing pathology are bound to become progressively less effective as someone gets older. It's obvious.
The next question we have to ask ourselves is: Why has humanity been so wedded to this insanely quixotic approach? One might say that perhaps there are no alternatives. (We'll see shortly that that's not true.) Another answer is simply that we have misdefined aging. And indeed, that is the case.
If you ask most people, "In what ways can people be sick?", they'll say, "There are communicable, infectious diseases. There are genetic diseases that a few people get. And there are the chronic, progressive diseases of late life, like Alzheimer's and most cancers.” And then they would say that there's this completely different phenomenon called aging, which consists of rather poorly defined phenomena like frailty.
The perception is that aging is so different from the diseases in this common taxonomy that it's essentially off-limits to medicine.
It’s a shame that we would think that. The correct view of the taxonomy of sickness is what I'm showing [in this next slide], which is exactly the same as the previous slide, in terms of the columns.
The only difference is where the black line is. That’s key for two reasons. First, the health issues in the third column [Alzheimer’s, cancer, etc.] are completely unlike those in the first column [malaria, HIV, and other communicable diseases]. There is no way that we would expect to be able to address [Alzheimer’s, cancer, or atherosclerosis] with the same kinds of medicine for [tuberculosis, malaria, HIV].
But [in my view of the correct taxonomy,] there is no difference between [diseases like Alzheimer’s cancer, etc.] and [frailty, sarcopenia, etc. — the ailments traditionally associated with aging]. It's just semantics. The issues in the third column are just the aspects of aging that we've chosen to give disease-like names to. That's a really important thing to take into account. It helps us see that we should be adopting a more preventative approach to the elimination of pathologies in late life.
This idea is not in any way original or my own. More than 100 years ago, people started thinking this way. They invented gerontology, which is inspired by the observation that in nature we see a very big variation in the rates of aging across different species. Even within a species, we see differences in individuals. The idea was that if we studied that variation, we might be able to understand it well enough to make our metabolism run more cleanly, so that it generates damage more slowly. That would be great, because it would postpone the point at which the damage reaches a level that causes pathologies.
But there's a bit of a problem with that [line of thinking].
Some of you may have written software in the past, and you may understand that this is the ultimate [example] of “spaghetti code.” There is no way that we're ever going to be able to manipulate this crazy network of processes that keep us alive in such a way as to stop it from doing the thing we don't want it to do — the creation of damage — without also stopping it from doing the things we need it to do to keep us alive. Not going to happen. And of course, this reflects only what we understand about metabolism. What really matters is what we don't know about how the body works, let alone what we don't even know that we don't know.
Luckily, there is a completely different approach. Remember: What we need to do is separate metabolism from pathology. We want to carry on being alive without having the side effect of getting sick late in life. I've shown that we can describe the link between metabolism and pathology as being divided into two processes, and I've also shown that we can't sever the link between them by breaking either process. But what we might be able to do is separate the component processes from each other. That's the maintenance approach — it’s damage repair. We might be able to periodically repair some of the damage that metabolism generates, so that even though it continues to generate it, the damage does not reach a level of abundance that’s bad for us. I think it is reasonable to call this the common-sense alternative.
In fact, we have already observed that it works. Take a simple machine, a car, that’s more than 100 years old.
It did not reach that age by being designed to last 100 years. It reached that age by being designed to last maybe 10 years, but then, through owners who fell in love with it and did comprehensive, periodic, preventative maintenance. In other words, aging is not a mystery. We already understand it well enough. It's simply the same thing as in a car. It's not some kind of emergent phenomenon like consciousness. And we already know, therefore, that comprehensive preventative maintenance works.
The body is, of course, a lot more complicated than a car. But how much more complicated? Not very much.
Seventeen years ago, I described the damage of aging in only seven words, as seven types of damage [cell loss or atrophy, division-obsessed cells, death-resistant cells, mitochondrial mutations, intracellular waste products, extracellular waste products, extracellular matrix stiffening].
What's most important is the fact that for each of these types of damage, we can describe a generic therapy that could potentially represent the maintenance approach — the way to repair this type of damage.
Within each category, there are many, many examples of subtly different types of damage in different tissues. But they can still be addressed through slightly different versions of the same therapy, which means that we can develop those versions pretty quickly. (I don't have time to go into that in any more detail right now.)
However, one thing I want to emphasize is that I’m not the only one saying this anymore. Five or 10 years ago, this was an argument that still needed to be made. But now it has been made. As an illustration, a paper came out only six years ago that is going to be, by far, the most highly-cited paper this decade in the whole of the biology of aging.
It's simply a restatement of what I said more than a decade earlier. (I don't care about getting credit — I get plenty.) The important point is that a divide-and-conquer, damage-repair approach is now a completely mainstream, orthodox idea.
The relevance of longevity is something that's worth talking about. If you look me up in the media, you will see that I get described as things like “the prophet of immortality.” It's a bit irritating, because we don't work on longevity, let alone immortality.
Longevity is a side effect of health. And yes, as I mentioned earlier, when people die, it makes people sad. But I think that the suffering before death is more important. There's an awful lot of it, and that makes people sad, too, including the people who are actually experiencing it. So to me, we're just doing medicine. There is a side effect that if we do medicine really well for the elderly, then on average, people are likely to live a lot longer. And I think that's a good thing, but it's still a side effect. So don't be seduced by [how the media constantly frames the issue].
Of course, the media harp on about it because of the ease with which it is possible to make a case against longevity.
People say, "Oh dear, where will we put all the people?", "It'll only be for the rich”, or “Won't dictators live forever?" These are very easy concerns to rebut. Last I heard, “dictator” was fairly high on the list of risky jobs; not a lot of dictators die of aging, and the ones who do organize their succession beforehand, so it's functional immortality.
[As for the argument that we will become bored if we solve the problem of aging], would you prefer to get Alzheimer's at the age of 80 or to be bored at the age of 150?
Even the concern of overpopulation [is easy to rebut]. This is a meaningful concern, but we know that the overpopulation problem we have today that's causing climate change is going to go away, because we've already got renewable energy that's cheaper than fossil fuels. The United Kingdom, for the first time since the industrial revolution, recently made more electricity from renewables than from fossil fuels. And that is something that we all know is going to continue. And artificial meats, desalination, and other technologies are going to raise the carrying capacity of the planet far faster than the population could conceivably increase, even if we completely eliminated all death.
We should focus on the fact that people do not like being sick. And we should focus on the fact that even if some of these problems arise as a consequence of solving the problem of aging, there is no way to argue that those problems will be worse than the [aging problem] we have today.
I'm going to finish by addressing the question of feasibility. It's very important for effective altruists to know that their money is spent well and making a difference. That's important to me, too, in terms of how I use my time.
About 10 years ago, it was unclear whether we knew enough about aging to know what to put money into. That’s no longer true. We’ve made substantial progress — enough to be sure that we're going in the right direction.
Over the past few years, the SENS Research Foundation has published breakthroughs in very high-profile journals. But more than that, we've been able to convince investors [of our progress] and spin out startup companies that are pursuing this issue with the benefit of considerably more money than what was available when research was only philanthropically funded.
And in addition to the companies that we've spun out, there are huge numbers of emerging companies that are aligned with us and doing other types of damage repair.
One example is Unity Biotechnology. They’ve been a poster child, because they were able to raise the kind of money that a biotech company would normally raise in phase three — when the company is [on the verge of receiving approval to bring a money-making product to market]. Unity received a huge amount of funding before they had begun their first clinical trial. That’s good news.
But when Unity announced a phase-one result last week — and it was a really good result — they experienced a 20% decline in their share price. (Phase one is all about safety, but if you're doing well, you look for efficacy as well, and they saw really good efficacy.) That's the problem with the private sector. It revolves around people trying to make money, irrespective of how they make the money. I think [what happened to Unity] demonstrates why we still need philanthropy.
SENS Research Foundation views itself these days as the engine room of the industry. We work on early-stage projects for as long as it takes to establish sufficient proof of concept to spin them out into startup companies. We're not the only ones. The Longevity Research Institute (LRI) is a new organization, also in the Bay Area, that's working in a more narrowly defined space. But they may grow, and, of course, there are going to be other organizations like this.
Philanthropy matters enormously in this. We believe that we can get all — or at least almost all — of the key technologies in rejuvenation biotechnology into clinical trials within a few years. About three years ago, we started saying we’d do that by 2021, and that has not changed.
But the key point here is that the things being funded effectively by the private sector are the low-hanging fruit. And damage repair is an inherently divide-and-conquer concept. You can't just focus on the low-hanging fruit. You've got to address all of the components. It’s more important than ever to make progress on the most difficult areas, and that is still a goal for philanthropy.
As some of you know, I wrote a book some time ago. Please read it if you want to know more about the biology.
Moderator: When it comes to impactful careers for bioscientists, how would you rate studying aging versus pandemic prevention?
Aubrey: That’s tricky, because pandemic prevention is certainly a huge area. The question is: Are there already enough people working in [pandemic prevention]? I honestly don't know. Certainly, there's a huge amount being done to build new technologies to develop antibiotics quickly, for example.
I think in order to answer that question, you need to look closely at the specific area [you’re considering going into] — whose lab you would work in and things like that — and look at the details of how much impact you could make. I don't think there's a simple answer.
Moderator: Thank you. And what relationship do you see between your work and transhumanism?
Aubrey: I don't see much of a link between my work and transhumanism. I don't like to be called a transhumanist. I do very much approve of the work that people who call themselves transhumanists do, whether it's working on AGI [artificial general intelligence], nanotechnology, molecular manufacturing, or things like that. But I believe that the word “transhumanism” is a huge albatross. It makes the general public think that we're all out to create a whole new species, rather than simply emphasizing the continuity of technological advances that people are generally happy with.
Audience Member: How much money do you estimate that we need to defeat aging?
Aubrey: No one can answer that question instantly, because the amount of money that one needs at the early stages to develop these technologies is much less than what is needed at the late stages. But the ease with which that money can be obtained is very different. Once [a treatment] has reached a clinical trial, then investment money pours in, because most of the de-risking has already happened.
So when I get asked that question and want to provide a headline, I say tiny amounts — a half-billion dollars over a period of 10 years would be enough. It's probably even down now to about a quarter-billion dollars. It's definitely still an order of magnitude more than what we have at the SENS Research Foundation (our budget is about $5 million per year), but it's a pitifully small amount of money compared to what’s generally spent on medical research.
Moderator: Thank you so much, Dr. de Grey.