“And it turns out I was right” Aubrey de Grey

Exclusive interview: Aubrey de Grey meets Longevity.Technology

“You shall not cut the hair on the sides of your heads, neither shall you clip off the edge of your beard.” Leviticus (19:27)

For those who have had any glancing contact with the subjects of aging, transhumanism or futurology, Aubrey de Grey needs no introduction.
In a world of new biotechs and new investment funds, with many of his ideas embedded in their founding principles, Aubrey de Grey is no longer viewed as a lonely or eccentric voice in his field. He is instead one of the oldest advocates for something that would, were it to come to pass, be an entirely new departure point for our species. And that, and maybe the beard too, could make him a unique character in the Longevity space: a prophet.

He sat down for an exclusive interview with Longevity.Technology to discuss his views.

Longevity.Technology: We’ve read a lot of very compelling reasons from you as to why we as a society should care about aging, but we’re very curious what made you care about it?
Aubrey de Grey: Nothing really made me care about it. It was always obvious to me that it was the number one most important problem in the world. It’s the thing that causes by far the greatest amount of suffering and everyone gets it. The astonishing thing was that other people didn’t think that way. In fact, I only discovered that others didn’t in my late 20s. I had gone through my entire life presuming that it was as obvious as the colour of the sky. It wasn’t something I would even have conversations about, so I’d never done the experiment to determine whether anyone else agreed.

Then I met my ex-wife, who was quite a senior biologist at the time. And I began to discover that, actually, people didn’t think that way, not even in biology. And hardly any work was being done to deal with this problem. So I thought “Well, that won’t do.”

Longevity.Technology: So why don’t people think about it? Is this an echo from a more religious time?
Aubrey de Grey: It isn’t explicitly religious, but I do think it’s a large part of why religion exists. The deeper reason is that aging is simply so terrible that we have to find ways to put it out of our mind and get on with our miserable lives. And that made perfect sense until I came along.

A few years ago, there was just no plan; there was no way for people to figure out how to bring it under comprehensive medical control. There wasn’t even a way to estimate how long it would take before we’d even understand the problem. It made sense to not get one’s hopes up and to put it out of one’s mind.

But, now that we can do something about it, that attitude has become irrational. It’s a huge part of the problem, because it keeps people in a mind-set that makes them strongly ambivalent towards the idea of doing anything about it. It limits the funding available, it limits the amount of effort that gets put in and it slows down the actual job.

Longevity.Technology: What is the SENS platform and why did you need to create it?
Aubrey de Grey: SENS stands for Strategies for Engineered Negligible Senescence. It’s a formal name for the way my organisation, the SENS Research Foundation, develops therapies for the diseases and disabilities of aging.

When I started working on the biology of aging, I spent a few years simply assimilating what was already known and what people’s beliefs were. But I had the huge advantage of having come in from a completely different discipline. (I first learnt how to work on really hard problems by training in computer science.)

I was able to see that there was indeed a very different, and entirely overlooked, approach to dealing with aging. And it was something the people who were studying it weren’t doing: that we should essentially be trying to repair damage in the body.

There was a general understanding of this, albeit stated in a variety of different ways. To be concise: aging is simply the lifelong accumulation of damage, and the body is set up to tolerate only a certain amount of said damage. Eventually it overwhelms us and we get sick and die. This was understood back then, but the prevailing view was to postpone that by somehow tweaking metabolism to make it run more ‘cleanly’ — in other words to generate damage at a slower rate.

But I realised that, actually, there was a much simpler and more effective way. And that was to repair the damage, after it had been laid down, but before it had reached the pathogenic level of abundance. And this was extremely heretical when I first suggested it, something that many people opposed and said was unscientific. The reason why they did so was because a lot of the technology and science I was bringing to bear on the problem wasn’t from gerontology, it was from other fields.

When I’m feeling frivolous, I like to compare gerontologists of that era to seismologists. What they studied was bad for you, but they had no idea whatsoever how they could actually do anything about it.

I stuck to my guns, stood my ground and people have gradually caught up and understood the kinds of things I’ve been saying all the time. Now it’s totally mainstream — orthodox — and people are reinventing the idea in slightly different language. So that’s all very nice.

Longevity.Technology: And you move the field forward by testing out previously unexplored areas for potential therapies, right?
Aubrey de Grey: I put forward a lot of damage-repair strategies in the early 2000s, and what we’re seeing now as a result of it is progress down the line in all kinds of therapies. Some of that progress is impressive enough to mean we haven’t needed to carry on doing it; we’ve been able to take these projects and spin them out into start-up companies that we’re able to draw in investment for from people who actually want to make money.

And it will not surprise you to learn that a great deal more of the money available comes from investors and not donors. This is extremely good for the health of these projects and the rate at which they’re going forward, but it does mean, however, that there are unexplored residual areas. And they’re just as capable of killing us on their own.

So what we do at SENS Central Research Foundation, with the help of philanthropic support, is we give those areas enough proof of concept until they can be spun-out and invested in. The support is woefully inadequate. We still work on a pitiful budget about $5 million a year. If we had $50 million, we could go several times faster.

“… a centrepiece project in-house is to put back-up copies of the mitochondrial DNA in the nucleus.”

Longevity.Technology: What undeveloped areas are you working on at the moments? 
Aubrey de Grey: One that really is a centrepiece project in-house (and has been for quite some time) is to put back-up copies of the mitochondrial DNA in the nucleus. For non-biologists who are reading, mitochondria are very essential parts of each cell that perform the chemistry of breathing. They combine oxygen with nutrients in order to extract energy from those nutrients. And, unlike any other part of the cell, the mitochondria have their own DNA – separate from the DNA of the nucleus.

But the process of extracting energy from nutrients using oxygen is chemically hairy, producing a load of by-products (in particular free radicals) that can damage the mitochondrial DNA and give it a really bad day. So the idea that we’ve taken, that was put forward in the mid 80s, is to essentially put copies of the mitochondrial DNA inside the nucleus, modified so that it still works in there, to shield it from this damage. It’s not as hard as it sounds, but it still is very hard!

People gave up on it… they thought it was too hard. I thought that they’d given up a bit too easily. And it turns out I was right – we had to work about ten years or so before we eventually got to the point of being able to publish a single paper on this. But we eventually got there a couple of years ago, and now we have a second paper in the works demonstrating that we have done most of the job.

Longevity.Technology: Do you have any others that you’re just starting out on?
Aubrey de Grey: We’ve only just begun a project using stem cells for Alzheimer’s disease. Normally we don’t do stem cell work, because other people are doing it very effectively without our help. And it’s a very established field with plenty of money. But, there are some areas of stem cell therapies that are very ambitious, alongside being rather difficult to justify to people who control public funds. So we’re running projects in New York with the Albert Einstein College of Medicine that look at enabling neuronal precursor cells.

These stem cells will eventually develop into neurons and migrate around the brain in a way they would not naturally do after being injected. This is something that is absolutely essential in order to ensure that cells get to the right place after they’ve been injected to repair the damage from Alzheimer’s disease.

Longevity.Technology: Not even your worst detractors would accuse you of not being forward-thinking. Do you see a role for nanotechnology and other tech solutions being brought under your rubric?
Aubrey de Grey: Sure, I can give a very general answer to that. I think the role of non-biological solutions to medical problems is already very substantial, and it will undoubtedly inexorably increase over time. And one of the biggest reasons why is because of miniaturisation. The smaller that you can make things, the more they can go to places that other solutions cannot reach. And that’s certainly happening.

And, certainly, the concept of molecular manufacturing to create nanobots is the ultimate limit of that. Very good work is going on in that space. I have no real sense for how rapidly this will happen. At the end of the day it really comes down, not only, to the rate of progress in that area, but the relative rate of progress in that area against alternative areas – the more boring wet stuff that we do.

“…I don’t regard the current maximum limits on Longevity as having the faintest of meanings.”

Longevity.Technology: Most researchers talk about pushing back a 40-year window – between the age we tend to live to (80) and the age we know from centenarians we could live to (120). You talk instead about the radical expansion of lifespan. Which technologies and therapeutics would you say hold that promise?
Aubrey de Grey: Yeah, I mean the idea that the maximum age that people can reach today – in the absence of medicines that haven’t been developed yet – is some kind of fundamental limit that would still apply in the presence of those medicines… I mean, that’s obviously just completely illogical, it makes no sense at all.

Technology is all about transcending what we see in the absence of that technology, including manipulating nature in ways that benefit humanity, so I don’t regard the current maximum limits on Longevity as having the faintest of meanings.

Longevity.Technology: So are there any areas of those technologies that you see that happening in? Or basically your answer is, once those technologies take shape, we will end up seeing centenarians who live longer and longer and longer until the previous records just mean nothing?
Aubrey de Grey: That’s exactly the answer, yes. The real thing to focus on is that this is not about Longevity at all – this is about health. This is about stopping people from getting sick when they get old, which is not a particularly controversial goal. We just know that healthy people tend not to die tomorrow. Being sick is risky and being healthy is not risky. We’re very lucky to have this side effect.

“I’m the only one who does not rely, for the bulk of their funding, on the public purse… we work closely together. I’m very good friends with all these people.”

Longevity.Technology: Other aging researchers take a much more taciturn approach than you do when making these pronouncements. Two interesting questions follow from that: Why are they so careful? And why are you so sanguine and bullish? You’re the only one in this space doing that.
Aubrey de Grey: Yeah, I feel really sorry for my colleagues, to be perfectly honest. I always understand where they’re coming from and what their constraints are. I try to work with them.

Here’s the problem: as with any field there is a relatively small number of people who are experts, and within that minority there is a relatively small number of people who are willing to talk to the media and speak publicly. And there will probably be no more than a dozen such people at any given time. And you’re quite right, out of those dozen such people, one goes out and tells it like it is. Why? Because I’m the only one who does not rely, for the bulk of their funding, on the public purse – the grants that come from a peer-reviewed application.

Peer-review for grant applications is a grim business, there is too little money. A typical gerontologist, certainly a typical scientist, goes up against around ten times more people than there is money for funding. So, of course, this means that the reviewers (who are determining which 10% of applications are approved) are constantly looking, desperately, for reasons to say no. Reasons they can adduce to justify saying, “We can tell this irresponsible person ‘no’ because they say things in public that inappropriately get people’s hopes up.”

That means that all of my colleagues have to be extremely careful not to get into a position where anyone could possibly accuse them of that kind of thing. I totally understand where they’re coming from, and they understand where I’m coming from. They’re very envious of me for not having to sell my soul to peer review. So basically, we work closely together. I’m very good friends with all these people. I do what I can do to take all the bullets that they can’t take. And to open doors, that they can then work through, with the considerably larger amounts of money they’re able to access by virtue of not being such a heretic.

Longevity.Technology: You’ve volunteered yourself as a human shield, then?
Aubrey de Grey: George Bernard Shaw said it in a different way. He said, “The reasonable man, adapts himself to the circumstances of his time. The unreasonable man tries to change the circumstances. Therefore, all progress depends upon the unreasonable man.” Yes, that’s me.

Longevity.Technology: If we look at the damage-repair theory that you base the SENS platform from, it should mean that the first therapies out of the gates will be skewed towards the damage that we can notice the most easily. What is that damage?
Aubrey de Grey: An important question that people ask me is that, “You’ve got all these types of damage that you’ve listed and you’ve got it all categorised into seven classes. Now that’s all very well, but surely, there’s going to be other types of damage that we haven’t noticed yet? After that we’ll have all kinds of new problems.”

That’s certainly not true. First of all, within the human species we already observe a load of variation, so it follows that there’s a certain amount of variation in the types of damage, including the relative rates within an individual. Which means that it would be completely astonishing if there another type of damage out there that was going to become prevalent only a few years later, but has so far been completely absent.

What’s much more likely is we will come across new types of damage, but they will fit neatly into the seven categories already enumerated. That’s certainly what’s been happening over the past twenty years since I’ve been talking about it.

But that makes sense, because the whole point of the classification is that generic therapies are required. When you have been able to implement a damage repair approach for a couple of examples within a given category, then you basically know what you’re doing. And when a new example comes along within the same category, you only have to make minor modifications to the therapies that you’ve already developed.

Of course, we can’t completely rule out that a new category number eight will come along in the future. But first of all, we can be very sure that it will only come along after quite a number of years, let’s say when we retire. Because otherwise, we would be seeing it already. And second of all, it’s very likely, just by looking at our biology, that these categories will be very similar to the ones that exist already. And if they’re not, we’ll see them through experiments. We’ll see them in monkeys that we are rejuvenating.

“… the investment community is involved in supporting the various start-ups … And because they’re early, they’re also high risk. So they attract angel investors, seed investors, people who are comfortable with high risk, high reward.”

Longevity.Technology: We’re also curious as to the involvement venture capital money will have in aging. On one side we’re seeing a lot of excellent trials from various startups at the tipping points of translation into human trials, then there’s a funding valley, and on the other side we’re seeing you in that ad for Barclays Wealth Management. So what about the middle? When and how will we start to see venture capital firms getting into Longevity, and do you have any ones to mention in particular who are getting involved? 
Aubrey de Grey: It’s happening right now! At the moment, the investment community is involved in supporting the various start-ups that have emerged over the past few years, covering the entire range of options for each type of investor. Of course, many of these companies are very early. They don’t need much money yet, because they haven’t entered clinical trials yet. And because they’re early, they’re also high risk. So they attract angel investors, seed investors, people who are comfortable with high risk, high reward.

And there are companies that have gone public already, like AgeX therapeutics, for example, which I work part time for, or Unity Biotechnology. These are companies that are floated on the New York Stock Exchange.

In between you do also have some bona fide venture capital. One company that I’m very close to, called BioAge, got its seed round from an Ivy League VC company named Andreessen Horowitz. And they got their Series A round from a consortium of three or four such companies. So investors at every level are getting involved at this point.

Longevity.Technology: How does pharma slot into all of this, we’ve heard and read a few interviews of you where you feel they’re really still holding onto old notions, instead of adapting to a preventative route.  Is that a view most of the pharma companies also hold?
Aubrey de Grey: There’s a big difference between what Big Pharma are saying and what they are doing. What they say, of course, comes from their primary focus – as very big companies – which is their shareholders. So they’re tailoring what they say around their share price and their quarterly balance sheets and all the rest of it.

But of course, what they do is internally prepare for the future. And they’re not stupid; I know perfectly well that the future is going to be very different; it will have a vastly greater emphasis on preventative treatments rather than treatment of people who are already sick. And it’s also going to have a much greater emphasis on treatments that are broader – treatments that affect a bunch of different future pathologies, rather than just one.

But I don’t blame them for playing two games in this way, everyone does. The other thing to mention is that Big Pharma don’t really do much of their own research anymore. They’ve given up doing it in favour of the alternative, which is keeping an eye on radical new therapies being developed by small companies, and then letting said companies sink or swim. And the ones that swim, that show a certain degree of proof of concept, they just go and buy. And that works perfectly well.

Longevity.Technology: So what would you say are the biggest challenges that remain for the industry? What technologies or companies are poised to solve them?
Aubrey de Grey: Well, the number one challenge is the one I addressed earlier: the most difficult components damage repair are of still not quite far enough along in terms of proof of concept to be investable, and therefore, are still being pursued only through organisations like SENS Research Foundation that are funded by philanthropy, and that funding is woefully inadequate. Without good ways to repair all of the types of damage that are accumulating, we will simply not see the full-blown impact of rejuvenation biotechnology. We will see some impact, for sure, but we definitely won’t see the real McCoy.

“… the big period of chaos and turbulence that will occur in the transition to a post-aging world is going to be right at the beginning.”

Longevity.Technology: What about the challenges the industry puts on those outside of it?
Aubrey de Grey: It’s extremely important that a large number of policymakers across the world and in various different sectors should actually be listening and paying attention to Longevity right now. It’s very likely that the big instability, the big period of chaos and turbulence that will occur in the transition to a post-aging world is going to be right at the beginning. And this could be earlier than you think, because I don’t mean, “at the point that the therapies have arrived” I mean, “at the point that the therapies become widely anticipated.”

In other words, the point when people start to take their heads out of the sand, and are no longer wedded to the policy of not getting their hopes up. When the science has moved forward sufficiently that it just becomes impossible to carry on thinking that it will never happen. And I believe that that transition of people’s expectations is highly likely to happen within the next five years.

Because it’s not going to take all that much more progress in the lab, in mice, than what already happened. And of course, I know, a good deal about what’s coming down the pipeline.

The reason I’m scared about this is because I’m talking about big-ticket items. The main things that people spend their money on, and the main decisions they make in terms of where their income goes, are all dependent on how long they expect to live. The premiums they pay want to pay on their health insurance, what their pension look like etc. And this is still an absolute wasteland. The good thing is that I do get invited to speak to banks and firms and insurance companies quite a lot. And so I’m, hand-over-fist, doing my best to educate everyone in this regard, but it’s painfully slow. There’s still a vast amount of ignorance.

Longevity.Technology: This is especially tricky with the trouble pension funds, and retirees, find themselves in, even if Longevity wasn’t going to be a thing, right?
Aubrey de Grey: Well any financial institution has ways to hedge. They can create a range of products and balance them so even if one goes south, another will do well. So I’m not too worried about that. But you can only hedge on certainties that you’re able to recognise. So if you hedge assuming that Longevity is only going to increase at the gradual rate it has in the past, you’re going to be totally screwed when you find out that you’re wrong. And, in particular, when your customers find out you’re wrong.