[MUSIC PLAYING]
SPEAKER: So I am introducing Aubrey de Grey,
who is the chief science officer of the SENS Research
Foundation.
And he is a major force in aging research,
and I'm very excited to hear this talk.
[APPLAUSE]
AUBREY DE GREY: All right, thank you all for coming.
Glad to see so many of you here.
Yeah, there's only five books left over there.
That's about-- there were 20 when we came into the room,
so hurry.
But yeah, and I'm happy to sign them
if you really want to be a terribly fanboy kind of person
later on.
All right, so yes, so I've got an hour,
so I'm going to try and tell you as much as I can about
what we do at SENS Research Foundation.
And why, and why it's important and why
you should be supporting it and how you can support it.
And there are various ways you can do that.
I'm going to start by giving you a really top-level idea,
because I know, obviously, most of you
don't have very much in the way of biology training.
I'm going to start by saying why I think this
is such an important problem.
This part of the world, Bay Area,
is really the epicenter of the effective altruism movement,
the movement that really focuses on rationally determining what
is the best way to spend money on humanitarian causes, what
gets the best bang for the buck.
And of course, people try to figure out
what the amount of suffering is that
is caused by this or that problem,
and what it would cost to do something about that.
And they try and figure it out from there.
And a lot of this comes down to the trade-off
between mean and variance.
In other words, between understanding how much good you
can do and understanding the uncertainty as
regards how much good you can do.
So high risk, high reward endeavors,
like pioneering technology, often
get kind of the short end of the stick when
it comes to effective altruism.
Because they don't really offer the confidence,
the certainty, that people like to see
with regard to knowing that what they're doing
is actually beneficial.
And the extreme end of that spectrum
is the situation where you don't know whether the problem is
solvable at all, whether--
it's not just high risk, high reward.
It could be 100% risk.
In other words, you know, zero chance of success,
however large the reward would be.
And the problem with that is zero times anything
is still zero.
So however valuable that the goal might be,
you wouldn't really want to go there.
And certainly the comparison between the defeat of aging
versus various other seriously high profile major issues
today, such as the ones I'm listing on this slide,
you know, that's quite a contrast.
Before I was a biologist, I used to work
in artificial intelligence research.
And the fundamental reason I did so
was that I didn't think that work was a terribly good thing.
You know, I think it's a great shame
that people have to spend so much of their time doing stuff
that they wouldn't do unless they were being paid for it.
And so I decided I wanted to fix that with automation.
And I worked in that area, actually,
in software verification, for several years
before I discovered that the obviously much more serious
problem of aging was actually being worked on very, very
little indeed by biologists.
And I thought that was a bit crap, really,
so I switched fields.
But when I switched fields, I realized-- in fact, actually,
this was actually part of the reason why I switched fields.
I realized that the people who were working on this, which
were, as I said earlier, only a very small minority
of biologists, were going about it
in a rather unimpressive way.
They weren't really going about it as engineers.
They weren't really breaking down
the problem in a structured manner the way
that a programmer might do.
And so that's what I tried to do.
And I started here.
I started with the question, well, look, 200 years ago,
even in the wealthiest countries, more than one-third
of babies would die before the age of one.
More than a third.
And of course in the rest of early life,
you know, in early adulthood, even,
there would be a lot of death.
Childbirth, especially, of course.
And we've pretty much entirely eliminated that now
in the industrialized world.
And of course, we're doing very well in that direction
in the developing world, too.
We've done it by really elementary means,
just by figuring out that hygiene was a good idea,
and by elementary medicines like vaccines and antibiotics.
And of course, even mosquito nets.
You know, these are tiny things.
And they work.
They've saved the most ridiculous number of lives.
But we've made virtually no progress
against the ill health associated with old age.
What's going on?
Why is it so different?
So most people would say that this is the answer.
Don't worry.
You're not supposed to be able to read this slide.
The point here is obviously just that there's
a lot of complexity.
An awful lot of different things go wrong with us late in life,
and they go wrong at more or less the same time, which
means, of course, that they interact with each other.
They exacerbate each other.
The whole thing is a little bit chaotic.
And so most people would say, well, this
is fundamentally what's going on.
The real reason why aging has remained so hard
to tackle with medicine is the sheer complexity
of the business.
The fact that there's so much going on,
it's just overwhelmed the ability of the medical research
community.
Now, there is a lot of truth in that.
That is definitely part of the problem.
But what you've got to know is that it's not
the main part of the problem.
There's a more fundamental reason
why aging has been hard to tackle,
and I'm going to deal with what that is.
I'm going to start by defining aging.
This turns out to be actually pretty tricky.
So [? Bjork, ?] who's hosting me today,
actually got an email this morning saying, listen,
we don't want to fix aging.
You know, we think it's a good thing.
We want to get older and more knowledgeable and all that kind
of stuff.
Of course we bloody do.
That's fairly obvious.
I mean, the point, obviously, is that we
want to get rid of the bad parts of aging
and thereby perpetuate and enhance the good parts.
So aging, for the purposes of this talk,
will mean the bad parts of aging.
So aging is not something specific to biology.
You can look at certain aspects of biology, especially
human biology, and you can say, well, in some sense,
they are emergent phenomena.
You know, consciousness.
You know, rocks are not conscious.
Cars are not conscious.
We knew that, right?
But aging is actually not an emergent phenomenon.
Aging is a phenomenon that is fundamentally
the same in living organisms as it
is in any man-made machine with moving parts,
like the car or an airplane.
It is simply a fact of physics that any machine with moving
parts is going to do itself damage throughout its existence
as an inevitable consequence of its normal operation.
It's just a fact of physics.
And that damage is going to accumulate.
And that's fine for a while, because any machine,
living or not, is set up to tolerate
a certain amount of damage.
And so that's why, for example, cars
work perfectly fine for a few years,
and you don't have take them into the garage.
And it's also why humans work pretty well for a few decades.
You don't have to take them into the hospital, either.
But eventually, the tolerable threshold of damage
is reached and exceeded, and that's
when things start to go downhill.
That's all that aging is.
And the reason I emphasize this is
because there is a very widespread misconception
in society that aging is some kind of mystery,
that it's some kind of enigmatic thing
that we absolutely don't understand and never can.
You know, it's somehow off-limits from medicine.
It's just not correct.
This is simply a really obvious and basic thing.
And we just need to get out of our heads
the idea that it's in any way mysterious.
We can actually describe it in just three words.
So I'm now obviously restricting myself to biology,
to living organisms.
Metabolism is the word that biologists
use to encompass all of the stuff
that the body does from one day to the next to keep us going,
keep us alive.
And metabolism creates damage, and damage accumulates
through our lives, even starting before we're born.
And eventually there's too much damage,
and you get the pathologies of old age.
Now, I've drawn these arrows in this rather curious way,
of course, to emphasize that what
we're trying to achieve with the work
that we're doing to eliminate aging
is to weaken the link between metabolism and pathology,
the link between being alive and being dead.
And there are various ways in which we might go about that.
But most of them are very misguided and essentially
a waste of time.
And I'm going to go through a little bit of why
that is before going on to what's going to work.
So what I'm showing you here is the answer that most
people would give to a very simple question, the question,
in what ways can one be sick, can people be sick?
In other words, give us a taxonomy of sickness.
Most people would say, well, OK, there's infectious diseases.
That's column one, communicable diseases.
Then there's column two.
There's congenital, genetic diseases
that some small proportion of us are unlucky enough to inherit.
Then in column three, there's the main problems
of ill health in the industrialized world today--
namely, of course, the chronic progressive
diseases of old age.
Alzheimer's, cancer, atherosclerosis--
those are the big diseases these days.
And then most people would say that way out
here in the stratosphere somewhere,
there is this other fourth completely different thing
which is not like diseases at all, this thing called
aging itself, which consists of these rather nebulous, rather
nonspecific phenomena, like frailty and sarcopenia, which
means the loss of muscle as we get older,
and immunosenescence, the declining function
of the immune system.
And most people will just feel that these things are
so different from diseases that we might as well not
even think about them in the same way at all.
You know, that they're kind of--
well, as I mentioned earlier, off-limits to medicine.
You know, they're kind of natural and inevitable
and all that kind of nonsense.
This is what people say.
They say, well, there's aging, and then there's
the diseases of old age.
These are different things.
Aging is somehow universal and natural,
and the diseases of aging are not.
That turns out to be completely incorrect.
The correct way to classify how you can be sick is shown here.
All the four columns now are the same
as they were on the previous table.
But the difference is that that big black line
is in a different place, between columns two and three instead
of columns three and four.
And that is so as to emphasize two key points, two
key misconceptions and errors in what people normally think.
The first error that people make that is
shown by putting the black line in the wrong place
is to think that there's some kind of fundamental distinction
between column three and column four--
in other words, that there really
are diseases of old age and then there's aging itself.
That's complete nonsense.
The only difference between column three and column four
is semantic--
that column three consists of the aspects of aging that
we've chosen to give disease-like names
to and column four consists of the aspects of aging that we
haven't.
That is all.
Everything in either column three or column four
is a consequence of having been alive a long time,
a consequence of the accumulation of an amount
of damage in the body of whatever type
that exceeds what the body is set up to tolerate.
That is all.
The other thing that putting the black line in the wrong place
causes people to think, which is wrong,
is to think that column three is rather like column one.
If you put the black line in the wrong place,
then you're going to look for cures things in column three,
ways to eliminate them from the body in very much the same way
that you might eliminate tuberculosis infections
or whatever.
And that, again, is obviously complete nonsense
when you remember that the things in column three
are side effects of being alive.
So basically, this is the result.
When you make that mistake, you go after the pathologies
of old age directly.
You try to eliminate them from the body by effectively
attenuating the right-hand arrow,
trying to stop the pathologies of old age from happening,
even despite the fact that the things that are causing them--
namely the damage that's continuing to accumulate--
is still accumulating.
And it's complete nonsense.
It's obviously complete nonsense.
There's no way in the world that this could ever work.
Because at the end of the day, if the damage
is continuing to accumulate, then anything
that attacks and addresses the consequences of that damage
is bound to become progressively less effective as time passes.
It's just a complete misconception.
It's a category error.
And yet billions and billions of dollars
are spent every year trying to do this,
trying to put not only medical research, but of course,
medical practice, trying to actually make this happen.
It's insane.
Now, I'm not the first person to point this out.
In fact, it's been more than 100 years now since people
started to realize, a few people started
to realize that this was a mug's game,
that geriatric medicine was never going to work.
And that's where gerontology came from.
Gerontology was inspired by two things.
Number one, the realization that geriatric medicine was never
going to work.
And number two, the observation that in the living world,
we see a great deal of variation in the rate of aging,
in the rate of accumulation of damage.
Different species age at very different rates.
Even within the species, different individuals
age at somewhat different rates.
So the idea was, well, if we study this really,
really, really hard, then maybe we'll
eventually figure out enough about how
metabolism generates damage that we
will be able to slow it down.
We'll be able to develop therapies that will somehow
clean up our metabolism so that it generates damage
more slowly, and thereby, we postpone
the age at which the damage reaches the Intolerable level
and pathology emerges.
Great idea, in principle.
You may, however, have noticed that gerontology has not
delivered the cure to aging any more
than geriatric medicine has.
And this is why.
Metabolism is rather complicated.
Since I'm speaking to a bunch of coders here,
I can immediately just say, well, OK,
this is obviously the ultimate nightmare
of uncommented spaghetti code.
Right?
This is just-- there's no way in hell that you're ever going
to be able to tweak this network so as to stop it from doing
the thing you don't want it to do--
namely the creation of damage--
without, at the same time, stopping it from doing things
you need it to do to keep us alive.
It's just not going to happen.
Unintended consequences are going to happen.
So you know, waste of time.
And unfortunately, you know, it took a while for gerontologists
to realize this.
But eventually they did.
I would say that by the 1970s, it was pretty much established
within the field of the biology of aging
that we were just not going to be able to get this approach
to work.
And so, actually, it went all the way to--
like it became unacceptable even to talk
about intervention in aging in a grant application.
Aging became this phenomenon, this field like seismology.
It was like, people who study earthquakes,
they understand that what they study is bad for you,
but they have no actual aspiration
to doing anything about them.
It's all about getting out of the way.
All right, but the thing is, there
was a bit of an oversight in all of this.
And the oversight was that there's
a third perfectly respectable approach
to dealing with this problem, which
is what I'm going to call the maintenance approach.
Or you could call it the damage repair approach.
And I'm trying to depict it using the same diagram.
Essentially what we have is the goal
is to weaken the link between metabolism and pathology.
And the geriatrics approach to do
that is to weaken the right-hand component
of that process, the link between damage and pathology.
The gerontology approach is to weaken
the left-hand side, the link between metabolism and damage.
But we don't have to do either of those.
What we can do instead is go in and periodically repair
the damage.
And of course, what that means is that we can leave metabolism
alone.
We can let metabolism generate damage at the natural rate,
and still, it won't reach the level of abundance
that causes pathologies to emerge.
So this is a fantastic way of doing what engineers do,
of sidestepping our ignorance, of figuring out
how to manipulate a system without actually understanding
it particularly well.
If we're not proposing to do anything
about the rate at which damage is created,
it's fine that we have such a pitiful understanding of what
metabolism actually does and how damage is created.
Similarly, if we're not proposing
to let damage reach a level of abundance
that causes pathologies to occur,
it's fine that we don't have much understanding
of the details of how those pathologies arise
from that damage and all the interactions
between the pathologies that I mentioned at the beginning.
It's fine.
We can just separate the two things from each other.
And it's not just common sense to you and me.
It's common sense to people in general, if you think about it.
Because hello, OK.
Right, because we already do it.
Remember what I said at the beginning,
that aging is a phenomenon of physics, not biology?
Well, here's a bit of physics for you.
Here's a car that is more than 100 years old,
and it wasn't built that way.
The people who built this car 100 years ago
would have been astonished at the idea
that any of the cars they were building would last that long.
They were built to last maybe 10 years.
But it turns out that we now how,
because cars are fairly simple, we
know how to do sufficiently comprehensive maintenance
on cars that we can keep them going just
as well as when they were built.
And now that we've got this 100-year-old car,
there is nobody who would say, oh, dear,
you know, well, we got them out to 100 years,
but there's no way we're going to get them to 200.
That's not going to happen, is it?
Everybody knows that we can push this out
as long as we like now.
So it's completely obvious to anyone
who takes aging seriously and doesn't actually regard it
as some kind of enigma, some kind of magic,
that this is what we should do to actually fix aging.
So you know, I say this.
I say at the end of the day, the only reason
that I have to go around the world giving these bloody talks
still, after all these years, is because people don't
want to hear this message.
It's been a long time since we realized that aging
was actually rather horrible.
Since the dawn of civilization, people
have had this dream of actually finding some way
to maintain youth in old age.
And we haven't done very well.
And the problem is, of course, that a lot of people
have been out there saying, oh, this is the solution.
And they've always been wrong.
So humanity has been suckered rather often.
Which means, of course, that there
is a great deal of reluctance to get one's hopes up now,
you know, to actually get into a mindset of saying, well,
maybe this time it's actually going to be true.
People, instead, they've gone the opposite way.
They say, well, OK, let's just believe that aging really
is a complete inevitability.
Let's kind of make our peace with it
and resign ourselves, and get on with our miserably short lives
and make the best of it, rather than being constantly
preoccupied by this terrible thing that's going to happen.
So of course, the way we do that, overwhelmingly,
is by making up these fantasies that pretend that it's
a blessing in disguise.
You know, that there's some kind of good thing about aging.
I call it the pro-aging trance.
Because it's a bit like being hypnotized.
You know, when I was a kid, when I was a student at Cambridge,
I went to a stage hypnotist's in which the hypnotist got
a guy on stage and told him, this is actually
your right elbow and this is your left elbow.
OK?
That's what they said.
He just got the guy to completely understand
and believe that his elbows were actually switched.
And then he said, OK, please touch your right elbow
with your left forefinger.
And then with a whole lot of writhing and wriggling,
as you can imagine.
And that was all very funny.
But that wasn't the point of the show.
The point was what came next.
What came next was the hypnotist says, OK, you can stop now.
And the guy stopped.
And the hypnotist says, right, you couldn't do it, could you?
And the guy said, no.
And then the hypnotist said, why not?
And what happened then is absolutely breathtaking.
What happens without fail is that the subject
will give a completely unhesitating, lucid, coherent,
grammatical answer to the question.
He will explain why he couldn't touch his left elbow
with his right forefinger.
And of course, the actual explanation
will have a hole in it the size of Canada.
You know, there will be absolutely no rationality
to the answer whatsoever.
So everybody will fall about it and it
will be terribly amusing.
But the fact is that the subject won't have a clue what's
wrong with what they're saying.
This was-- I mean, this was at the University of Cambridge,
right?
A bunch of undergraduates with very high academic achievements
and everything like that and high opinion
of their own intellect and their own rationality.
And the guy's just sitting there with all his friends
cackling at him, and he just doesn't have
a clue what he's saying wrong.
So to me, it's exactly like that.
You know, it's unbelievable.
So I realize that at this point, all I've done
is told you what's the common sense
approach to tackling aging.
What I haven't done is give you a feel for how difficult it
actually is.
Even if it's a common sense approach,
it could be awfully hard, right?
And therefore not really worth getting
too optimistic about yet.
So that's what I need to address next.
I need to actually tell you.
I've told you that we're sidestepping our ignorance
of metabolism-- wonderful.
And we're also sidestepping our ignorance
of pathology-- also wonderful.
But what we're definitely not sidestepping
is the complexity of the damage itself.
We absolutely can't implement this maintenance approach
unless we can characterize what that damage is and figure out
ways to repair it, to eliminate the damage
and restore the structure and composition of the body
at the molecular and cellular level
to something like how it was at a younger age.
That's what this is all about.
So can we actually do that?
Well, this is really where the good news begins.
17 years ago, when I first started thinking about this,
thinking about the problem in this way,
the only reason why I felt optimistic
was because I was able to derive a rather concise taxonomy,
classification of damage.
So that's what we have on the left-hand side of this table.
And all the seven things you see there--
as you can see, very clear, concrete, down-to-earth,
real biological phenomena.
Cell loss-- what's that?
It's just the case of cells dying and not
being automatically replaced by the division
and differentiation of other cells.
So of course, if that happens, then progressively the number
of cells in the affected organ will decline,
and eventually you'll end up with not enough cells
for the organ to be able to do its job.
An example of an aspect of aging that is mainly
driven by that type of damage is Parkinson's disease,
which is mainly caused by the loss of a particular type
of neuron called a dopaminergic neuron
in a particular part of the brain called
the substantial nigra.
And sure enough, you know, that's bad for you.
It happens a little faster in some people than others,
and that's why some people get Parkinson's and some people
don't.
But all of us have lost at least a quarter
of our dopaminergic neurons that we
had as young adults by old age.
So it's a general phenomenon.
And I could go down the list.
I won't do that now.
I'll address one or two of these later on in other ways.
But basically, [INAUDIBLE] all the way down.
The good news, of course is not just
that we can do this classification,
but that we can write the right-hand side of this table.
The purpose of the classification
is precisely because for each of the categories,
there is a generic approach to actually eliminating
the damage, to fixing the problem.
When I say generic, what I mean is that there will definitely
be differences at the details of how
we use this generic approach to address
different examples within a given category,
but only the details.
So if we look at cell loss, of course
you will already know what the fix is.
It's called stem cell therapy.
That's exactly what stem cell therapy is.
We simply prepare-- pre-program, if you like-- cells in the lab
into the right state so that when
we inject them into the body, they know what to do.
They know how to divide and differentiate
to replace the cells that the body is not
replacing on its own.
Parkinson's disease, coming back to that,
you know, that's exactly what's being done now.
The first time this was attempted was 20-odd years ago,
and we were hopeless back then at the preprograming step.
We didn't know what to do to get stem cells into the right state
before we injected them.
And sure enough, the process only gave any real benefit
very occasionally.
Most people didn't benefit.
But the ones who did benefit didn't just
benefit a little bit.
They were completely cured.
Just last year, there was a paper
that came out celebrating the 25th anniversary
of the first successful, the first real responder
of the first clinical trial in this area.
And this is a guy who was taken off
all other medications for Parkinson's after a couple
of years, has had no subsequent stem cell
treatments or anything--
no Parkinson's disease.
25 years.
So this is real.
And now that we're much better at the preprogramming of stem
cells in the lab, people are very much more confident
that we can actually do this reproducibly now.
So there are quite a lot of different clinical trials
against Parkinson's that are actually just getting
going now in preparation.
And there's a lot of optimism.
So that's the kind of thing that we can expect when we really
repair damage.
Now, you may ask yourself, well, OK, well, stem cell therapy
is a very well-respected area.
The right work is being done.
It's already moving through clinical trials.
Why does Aubrey de Grey feel it's
necessary to go around the world giving all these talks
and drumming up enthusiasm and so on?
And the answer is because the other six categories
I'm telling you about here are much,
much less well-appreciated.
That's why SENS Research Foundation exists, in fact.
We exist because all of the other categories
are just as important as cell loss,
but yet the ways to fix them are either just-- hardly anyone
understands that they could actually happen at all,
or else they're just not understood well enough, they're
not appreciated at how important they are, or whatever.
So we spend a lot of effort and a lot
of money trying to develop these things at the early stage,
proof-of-concept level, so that we can get them to the point
where the rest of society and the rest of the research
community takes them seriously.
Now I want to draw your attention,
before I go to the next slide, I want
to draw your attention to the bottom line here.
Because you may be thinking to yourself, well, hang on,
how does Aubrey know that this really
is an exhaustive classification, and that there
isn't some category number eight and number nine that's
been overlooked?
And of course, that's a very important question.
And we definitely cannot say that we 100% know that there
are no further categories.
We've been looking.
That's for sure.
And more than that, I've been going out there making trouble,
you know, generally making a nuisance of myself,
and challenging my colleagues to come up
with things that break this classification, things
that fall outside of it.
And you know what?
I'm getting away with it.
I've been doing it for a long time now.
So of course, that's only circumstantial evidence.
But it's really quite strong circumstantial evidence
that we seem to be on the right lines.
Not only that, the approaches on the right-hand side
of this table, the various repair methodologies that we
are focused on, have also not had to change over the past 15
years.
We have been pursuing them, of course,
and we've made progress in all of them.
And some of them have become easier
as a result of nice surprises like the development
of new technologies like CRISPR and induced pluripotent stem
cells that have shortened the time line to development
of these things.
But there have been no examples of bad surprises,
of cases where we find that this or that approach
is not going to work because of this or that new discovery.
So that's, again, really good news.
I'm going to give you a little bit
of a feel for this at the level of the actual benchwork now.
And as I mentioned earlier, of course,
you're not biologists, so I don't want to get too heavy.
But I do want to make sure that you understand I'm not totally
bullshitting you.
So let me talk a little bit about atherosclerosis.
Atherosclerosis, of course, is the number one killer
in the Western world.
And it consists of the accumulation of fatty deposits
in our major arteries, which grow and grow
and eventually burst and cause heart attacks and strokes.
So we'd like that not to happen.
That's for sure.
Now, the beginning of atherosclerosis
is depicted on this slide here.
This is a micrograph of part of a cell called a foam cell.
So what is a foam cell?
A foam cell is a cell that used to be
a perfectly healthy self-respecting white blood
cell, a macrophage.
That macrophage went into the artery wall
with the goal of cleaning up detritus that was stuck there.
It just happens.
That's one thing that macrophages do.
They're very good at it.
The detritus is mostly made of cholesterol, it turns out.
And cholesterol gets a bad rap, but it's a vital molecule.
The body needs a lot of it.
And macrophages know exactly what to do with cholesterol.
They know how to reprocess and repackage it and export it
so that it can be reused.
That's all wonderful.
But unfortunately, there is a small concentration
of contaminant within this detritus.
Most of that contaminant, the mass of it,
is actually oxidation derivatives, chemically
altered cholesterol that has become
chemically different and, in various ways, not amenable to
processing by the macrophage.
So instead of processing the cholesterol,
this oxidized cholesterol poisons the macrophage.
And it gets like this.
The lysosome, this part of the cell which
is very important in this processing business,
it becomes full of fat, basically.
And then the rest of the cell fills up
with these globules of fat.
You can see them.
So that's the beginning of atherosclerosis.
Foam cells happen.
You get more and more of them.
They start to basically get angry,
and the cells around them get angry,
and more macrophages come in to solve the problem.
But they can't, so they become part of the problem.
And that's how atherosclerosis progresses.
So what can we do about this?
Well, of course, people have tried a bunch of stuff.
One approach is surgery.
Go in and ream out these arteries,
and try and get rid of this fatty stuff
so that it doesn't accumulate enough to burst and cause heart
attacks.
And that's pretty crude, really.
And it doesn't work terribly well.
The other alternative that people have tried a lot
is statins.
Statins are drugs which reduce the rate at which the body
synthesizes cholesterol.
And that kind of makes sense.
If you do that, if you reduce the amount of cholesterol,
you're going to reduce the amount of oxidized cholesterol.
So you're going to slow down the poisoning of macrophages.
But as I mentioned earlier, cholesterol
is a rather important molecule.
We can't do without it.
So there's only so much that you can push that kind of approach.
And sure enough, statins have bad side effects.
What do we actually want to do?
Common sense, again.
What we actually want to do is go
after the actual problematic reagent, which
is the oxidized cholesterol.
And in particular, what we might like to do
is give macrophages the enhanced ability
to break down oxidized cholesterol,
or process it in just the same way
that they can naturally process normal cholesterol.
If we could give them an extra enzyme,
for example, that just allowed them
to degrade oxidized cholesterol, then bang.
You know, they wouldn't be poisoned by it anymore.
So that's exactly what we set out to do.
More than 10 years ago now, we decided
to find another species which already had an enzyme to break
down oxidized cholesterol.
Turns out that it's fairly straightforward
to find bacteria that can break down more or less,
anything you like, so long as it's organic.
And this has actually become a really important
commercial endeavor.
It's called bioremediation.
This, of course, is not a biomedical thing.
This is for environmental contamination.
You find bacteria that can break down TNT, for example.
Then you can just spray them over a disused airfield
that you want to build a housing estate on.
And the TNT's going to go away, and you'll
be able to build your housing estate.
This actually is done in the real world.
So great.
But our goal is not to spray bacteria into the body,
because that might have side effects.
Our goal is to find these bacteria,
but then to identify the genes, the enzymes that they have,
that allow them to break down this toxic molecule,
and then put that gene into human cells,
modified in such a way that it still works,
despite the various structural differences that
exist between bacteria and mammalian cells.
And it turns out to work.
So step one it's pretty easy, finding the bacteria.
Step two is also pretty easy, finding the genes
that the bacteria have that give them the capacity
to break down the stuff.
Step three is actually really hard,
tweaking the gene so that it still works in human cells.
But we managed it, a few years ago.
This is the key figure from the paper
where we reported this success.
Essentially what we're seeing here
is each group of bars is a different concentration
of the toxic molecule 7-Ketocholesterol, which
is a particular type of oxidized cholesterol
And within each group, what you've got
is the right-hand bar is engineered cells.
And all the others are what are called Negative Controls.
So for example, cells that don't have the enzyme.
Or they've got the wrong enzyme.
Or they're got the right enzyme, but it's not
been modified so that it goes to the right part of the cell,
for example.
And the height of the bar is simply the health
of the cells, the viability.
So the fact that the right-hand bar in each of the groups
is taller than the ones to its left, that tells you
that for each of these various concentrations of the toxin,
we are protecting the cells, by introducing this gene.
And this is, of course, quite promising results.
And it's being taken forward now into mouse models.
And we would hope that this will be
a much more effective approach to stopping people
from getting heart attacks and strokes than anything that's
around today.
So I'm going to address a few things you may be thinking.
So first of all, some of you may have come across my work
before.
Actually, hands up.
Yeah, hands up, anyone who's actually
seen a talk of what I've given in the past.
All right, jolly good.
Out good.
Nearly half of you.
All right.
So some of you may know that when I first
started putting these ideas out there, a lot of people
didn't think much of them.
A lot of people were quite derogatory.
And that's kind of no surprise.
Because the fact is, as I've already emphasized,
I was bringing together a lot of new ideas that
had never been brought into gerontology before.
In fact, you've just seen one, which
had never been brought into anything biomedical before.
It was only used for environmental contamination.
So there was a huge amount of education that had to occur.
I'm sure you appreciate that science
is a very Balkanized field, that people think they
know what they need to know.
They have a particular area of expertise that they're good at.
And they think they know what's relevant to that.
And they won't really take the trouble
to learn very much about things that they
don't think are relevant.
And it's pretty hard to break that down.
So it took, I'm going to say, the best part
of a decade for me to actually get
my colleagues, the predominance of my colleagues, to the point
where they actually understood that what I was saying
was not complete nonsense.
But it worked.
I really did get there.
First of all, we've published a lot.
We've actually got a lot of papers
out there in the academic literature,
including in high-profile journals,
demonstrating key proof-of-concept steps
towards getting these things to work.
So that's one kind of community recognition.
That we've got an advisory board,
consisting of a large number of extremely
high-profile world-leading scientists in all
the relevant areas.
These are not the kinds of people that publicly
endorse stuff that's bullshit.
So this is actually quite important.
But what's most important of all,
is that the idea is being reinvented by other people now.
So this paper came out four years ago.
And it's the identical same idea.
I mean, they decided to divide everything
into nine categories instead of seven.
But it's exactly a divide-and-conquer,
damage-repair approach.
Here are their corresponding sections.
Their graphics are a bit better than mine were.
But the fact is, it's identically the same idea.
And the difference is that this paper
was written by [INAUDIBLE].
And it's being cited, literally still, but once every two days.
This is probably the single most influential paper
in the whole of gerontology as of now.
And it is identically the same idea
that I put forward more than a decade previously.
Now, you know, it would be nice if I
would get more of the credit.
But that's really not what bothers me.
The fact is that this is now completely mainstream
and orthodox.
And any misapprehension that you may
have as a result of the kinds of things
that gerontologists were often saying about these ideas
10 years ago should be forgotten.
Because they're no longer saying that.
This has now become something totally accepted.
Second thing is to do with the magnitude
and the proximity of this work.
And this is something that I feel
I do need to address, especially with an audience like this.
Because this is something that polarizes
opinion a huge amount.
First thing I want to say is, people get terribly exercised
about the idea of living longer being scary.
You know?
And of course, a large part of what they are basing that on
is the idea that living a lot longer
might entail living a lot longer in the same state of health
that we currently associate with old age.
Which of course, is considerably less fun
than the state of health that we currently
associate with early adulthood.
So let me be perfectly clear.
There is zero chance, zero chance, that any of this work
will ever deliver that kind of life extension.
The only way that we are ever going
to get people living substantially longer
is by keeping them truly, genuinely youthful for
substantially longer.
It is always going to be risky to be sick.
So do not worry about that.
The question though, is how much longer?
I mean, in a way, medicine always
has this side effect, right?
After all, most people die of being sick.
So if you can help people not to be sick,
you're, on average, going to have them live longer.
Makes sense.
The question is, how much longer?
And it turns out that it might be quite a lot.
So the therapies that I've told you about so far, I believe,
have a respectable chance of giving us an additional 30
years or so of extra life.
And of course what I'm saying, healthy life.
Now, that's a lot.
It's a lot more than what we can do today.
But it sure isn't immortality, or any of the other words
that the media tend to like to associate with my work.
So what's the big deal?
That's great, but so what?
People are then going to get sick and old and dead, same
as before.
Right?
I mean, we've already extended the average lifespan
by more than 30 years in the past 100 years.
So you know, what's the big deal?
The big deal is the thing that I've called Longevity Escape
Velocity.
Which to a software engineer is a ridiculous straightforward
concept.
It simply is that these are rejuvenation therapies.
Therefore, they will be applied to people who are already
in, let's say, middle age.
Let's say, 60 or 70 at the time that the therapies arrive,
those people will be rejuvenated such
that they won't get back to being biologically 60
until they're 90.
Because that's the 30 years I'm talking about.
But we've bought that time.
In that 30 years, we've been able to improve
the quality, the comprehensiveness,
the convenience, the cost, but especially
the comprehensiveness of these therapies
so that the same people that are now 90
can be really rejuvenated.
Even though the damage that their bodies contain
will be the difficult damage that the original therapies
don't work on.
Nevertheless, some of it will be amenable to repair
by the new therapy--
let's call it sense 2.0--
30 years down the road.
So all we've got to do is improve the comprehensiveness
of the therapies by a sufficient rate
to stay one step ahead of the problem.
And the faintest analysis of what that rate actually
would be will tell you that it's tiny.
It's vastly lower than the rate that we always
see in the incremental improvements of technologies
once the initial breakthrough has been made.
So Longevity Escape Velocity is the reason
why I believe that the first person to live to 1,000
is probably less than 10 years younger than the first person
to live to 150.
And why the first cohort, most of whom will live to 1,000
is probably only 10 years younger than the first cohort,
most of whom will live to 110.
So these are obvious things.
But talk to biologists about this?
Especially gerontologists?
They will, almost all of them, run away very, very fast.
Because first of all, "it's not science."
Of course it's not fucking science.
It's technology, all right?
I knew that.
But the fact is, also, it's politically incendiary.
Gerontologists with reputations to maintain
and tenure to obtain and grant applications to submit,
they do not want to be associated with things
that the public haven't been able to get their heads around.
And let's face it, the public aren't very good at math.
And they're not very good at things like this.
So the fact is, it's a very hard political sell right now.
But I believe that it's better to tell the truth about what
we can expect from anti-aging medicine
of the foreseeable future, than to try
to sweep it under the carpet.
I believe that the right thing to do
is to actually say, look, yes, we
are going to be able to keep people youthful indefinitely.
Because we are going to improve these therapies fast enough.
And to say yes, that's a good thing,
and not to be cowardly about it.
Now, the other thing to point out
is that this is coming quite soon.
I believe that we have a 50/50 chance
of getting these technologies working within about 20 years.
Just so long as there is enough funding
for the really early stage research that's
happening right now?
Now of course, I know perfectly well
that this is pioneering technology.
And like any pioneering technology,
the time frames are ridiculously speculative.
There's certainly a 10% chance that we
won't get there for 100 years.
Because we'll hit problems that we haven't thought about yet.
But so the hell what?
You know what I mean?
50% chance is quite enough to be worth fighting for.
The thing about Longevity Escape Velocity
though, is that even though it is a concept
that gerontologists hate, as a concept
that the public doesn't get, and just kind of feels intuitively
it can't be true.
Nevertheless, it's only a matter of time
before people do get it.
It's so simple that people are just going to get it.
And I believe that that's probably
going to happen within the next few years.
I believe that there's going to be a real sea
change, a real tipping point in public attitudes,
public opinion, public understanding
of this whole field.
And it's going to happen soon.
And that's rather important to take into account.
Because what it means is that we have the responsibility--
those of us who do have a bit of intelligence
and can understand this already--
we have the responsibility to act now,
in whatever way we can, to minimize the turbulence.
You know, the sheer magnitude of the shit
that's going to hit the fan when the world realizes all of this.
We have to try to figure out how to maximize
the humanitarian benefit from all of this,
to maximize the number of lives saved,
and thereby, to get these technologies out there
as quickly as possible.
And a lot of that revolves around anticipating
these changes in public attitudes.
Let me explain why I say that.
At the moment, when you talk to people about it
and you say, how long do you want to live?
Would you want to live to 150?
Most people will say no.
If you ask them that question in an unadorned manner.
Even if you asked them the question,
do you want to live to 150 in a truly youthful state of health,
they will still mostly say no, largely
because they won't take the question seriously.
They won't really believe that you mean
what you say by the question.
That's how deep-seated and entrenched the belief
in the inevitability of aging really is.
Which means that when people are forced
to think about the consequences of truly eliminating aging,
they're very, very bad at it.
They will come up with this or that potential problem that
might be created as a consequence of fixing
the problem we have today, the problem of aging.
And then, two things will happen.
Number one, they will immediately
presume that the problem was insoluble,
and it's going to be far worse than the problem of aging.
And number two, they will immediately
switch their brains off and refuse
to consider the possibility that we might have a way to solve
this other problem too.
So for example, almost every talk I give,
and almost every interview I give, people will come up
and they'll say, where will we put all the people?
[SIGHS]
And you know, I've been giving perfectly simple answers
to this question for God-only-knows how long.
And nobody challenges the answers.
The standard answer, the best answer is simply
other technologies, like renewable energy
and artificial meat and desalination and so on,
are going to be increasing the carrying capacity of the planet
far more rapidly than the population of the planet
will increase.
Therefore, the population stress that the planet is currently
experiencing will diminish, whether we cure aging or not.
That's the obvious answer.
Really obvious.
And no one ever says, oh, that isn't true.
They just let it go in one ear and out the other.
And the following day they'll come back,
and they'll still ask the same question.
It's extremely frustrating, as you can probably tell.
And it's same with all the other nonsense.
I mean, one great example is that people will give
this overpopulation concern.
And the same people, in the next breath,
will say, oh dear, it's only going to be for the rich.
I mean, how the fuck can you not see
that these things are mutually exclusive?
So I mean, it's very frustrating, as you can tell.
And you know, last I heard, dictator was fairly high
on the league table of risky jobs.
Most people don't really die of aging.
And I mean, boredom.
I mean, my friend Brian Kennedy's
had a good one on this.
He said, look, if I've got the choice of getting Alzheimer's
when I'm 80 or being bored when I'm 150,
I think I know which one I'm going to choose.
And you know, a sense of proportion
just does not come into the way that people
address these questions.
It is absolutely embarrassing.
So obviously I don't have much time for this nonsense.
[LAUGHTER]
I feel that it's important to go out there and be positive,
and say to people, listen, for Christ's sake,
do you want to get Alzheimer's?
Do you want anybody else to get Alzheimer's?
Cancer?
No, you don't.
So consider a world in which nobody does.
get those things.
That would be quite nice, wouldn't it?
And you'd have a situation where the elderly were still
able-bodied and they were able to contribute wealth
to society.
So everybody would be ridiculously more prosperous.
And they would have the energy to explore novelty,
so they would not get bored any more
than a young person get bored.
When they're bored they go and find something new to do.
I mean, Jesus.
So that's enough of the rant.
I'll come back to another rant shortly.
But before I do that, let me just actually talk
a bit about the spin-outs that we're doing.
because we started out as a nonprofit, many years ago now.
And the reason we did was because the work
that we were doing was so early-stage,
that there was no way it was investable.
Even in Silicon Valley, where obviously we've
got an nicely high density of visionary investors.
But that's changed over the past few years.
We've been able to push some things far enough along,
in terms of proof of concept, that we have
been able to spin them out.
Let me just give you a few examples.
This is a company that's raised, so far, about $5 $5.5 million.
It's looking at macular degeneration, the number one
cause of blindness in the elderly.
Actually, pursuing very much the same approach to it
that I already outlined in relation to atherosclerosis.
Though in this case, the target is not oxidized cholesterol.
It's something completely different.
So that's pretty good news.
Another example is a company came out of Texas for work
that we funded for several years.
And this is to do with what's called amyloidosis, which
turns out to be a very important reason why
the extreme elderly people over the age of 105, 110, this
is what most of them die of.
We've got a company called [INAUDIBLE],,
which was started by the person who used to be our Chief
Operating Officer.
It's working on organ cryopreservation,
on a new method for freezing organs in such
a way as to basically do no damage to any of them
by crystallization or anything like that,
so you can warm them up again and stick them
into another person.
And this is something there has been
quite a holy grail of organ transplantation
for a long time.
But this group have now figured out how to do it.
And again, they've received only seed money so far.
But they are moving forward very rapidly now.
Another example is a company called Ocean, which
is looking at senescent cells.
Senescent cells, the type of cell
that gets into an aberrant state and does more harm than good
but doesn't go away.
And this is a way of getting rid of them.
It's a bit more controllable than the drugs
you may have heard about that other companies are
looking for.
Now out of that, the fact is, we're just around the corner.
And we are two miles from here.
I cycled here today.
So the fact is, you guys, yourselves,
could make a difference.
And any of you want to come and visit,
you're always very welcome.
I'll give you my email address at the end of the talk.
You can get in touch through the people here
who are already in contact with us and are already donating.
I mentioned a fact of altruism at the beginning of the talk.
I'm going to mention it again.
That number I've got on this slide, $1 per life,
is a fairly conservative estimate.
You can do these numbers.
You can just say well, OK, look.
How much is the current shortage of money slowing things down?
And of course, that's subjective.
But my current estimate is probably about 10 years.
That we could speed up the defeat of aging,
the achievement of Longevity Escape Velocity
by about a decade, just by getting this work
done at a speed that is not limited by financial resources.
So how much financial resources are needed to do that?
We just need one more digit on our budget.
That still means we'd be looking at 1% of [? Calico's ?] budget.
We need about $40 million a year.
$40 million.
I mean, that's a tiny amount.
And we could go, I'm going to say,
three times faster in the initial few years anyway.
And I think yeah, we could take a decade off the time involved.
So we're talking about half a billion lives.
That's about how many people die of aging in a decade.
And we're talking roughly $40 or $50 million
a year for 10 years.
So it comes out at around $1 per life.
And if you do that same calculation
for anything else, mosquito nets, whatever you like,
you don't get that number.
You get a number that's much larger, in terms
of number of dollars per life.
And that's, of course, just presuming
that the life is the same.
Which, of course, it isn't.
Because what we should really be calculating
is the number of additional healthy life years, which
is essentially indefinite in the case of defeating aging,
whereas it's definitely not indefinite for anything else.
The key point is the last line.
The number of dollars per life is
going to go up as time goes on.
The earlier stages of this work are always the time
when you can make the most difference with a given
amount of financial backing.
So now is the time when you can make the most difference.
This is the book I wrote, which there is one left over
on the table over there.
But obviously, we're perfectly happy to provide more of them.
I wrote this about 10 years ago.
And that might suggest to you that it's out of date.
But luckily, even though there has
been a huge amount of progress over the past several years,
the progress in question has been very much
what we expected it to be, what we've predicted it would be.
As I mentioned at the beginning, we
haven't had any nasty surprises.
So in that sense, the science is still very much
what it should be, and I very much recommend it.
It's written for non-specialists.
In other words, it doesn't have any real reliance
on biomedical jargon.
But at the same time, it is pretty dense.
You won't get through it in one sitting.
And I'll stop there.
Thank you.
And I'm happy to answer questions.
[APPLAUSE]
I don't know whether people can just shout
or whether they need a microphone
for the recording or what.
SPEAKER 1: They should have a microphone.
AUDIENCE: Hi my name is Evan.
Thank you.
Great talk.
Just a quick question on the fundraising piece.
My sense is that there is a lot of money
out there, if you had branded like, cancer research
or Alzheimer research, there might be other dollars.
How What are your thoughts on just maybe rebranding and going
after different there.
AUBREY DE GREY: Yeah.
So we thought about that, of course.
The issue though, really is, we have to do two things.
On the one hand, yes, we absolutely
have to get people to understand that this is a medical problem,
and that this is not something in the stratosphere,
as I mentioned at beginning.
But on the other hand, we also have
to demonstrate that the approach that we want to take,
which is substantially different from what other people are
taking, is much more likely to succeed.
And if we talk, for example, about Alzheimer's, then we
start out in a position where we are
competing with the established anti-Alzheimer's community.
And people are going to say, look, if this is worth doing,
then surely the Alzheimer's Association
is going to be funding it already.
And therefore, since they're not,
it must not be worth doing.
So it's quite circular.
But what it means is that we have to start off
by telling it like it is, in terms
of a taxonomy of sickness, and saying,
listen, think about aging in a new way.
And then break that down into what is common sense, what
makes sense about it.
There was a question over here.
AUDIENCE: So how about nuclear genomic mutations, in terms
of mitochondrial mutations?
I mean, that goes at the slower rate.
But in the end, that's what drives cancer, right?
AUBREY DE GREY: You want to know about mutations.
OK, well, mitochondrial mutations
are one of our seven strands.
And unlike the other six strands,
mitochondrial mutations cannot definitively be linked to any
particular pathology of old age in the same way that,
for example, molecular waste products can be linked
to atherosclerosis.
Nevertheless, there's plenty of circumstantial evidence
that says we need to fix them.
And so what we're doing is putting backup copies
of the mitochondrial DNA into the nucleus, modified
in such a way that it works.
This is an idea that was first put forward in the 1980s.
People basically gave up on it, they decided it was too hard.
We decided they'd given up too easily.
We were right.
It took us 10 years to prove it, but we had a paper
out a year ago, which was a great breakthrough compared
to anything that had been achieved so far.
And we're chugging along.
We're going to get there now.
So that's good.
Nuclear mutation, because with a nuclear genome,
different matter entirely.
So in one sense, of course, we're
very much tackling those, in the sense that one
of our other strands is cancer.
We don't want cells that divide when they shouldn't.
And we have a particular approach to going about cancer.
And maybe other approaches will work.
The question then is, if we don't
have to worry about cancer, if we've got a fix for cancer,
then do nuclear mutations still matter?
And it looks very much as though no, they don't.
The abstract way of looking at it
is to say, well look, one cell can kill you
if it gets the wrong constellation of mutations,
just by dividing and dividing and becoming a cancer.
Whereas anything else, anything that does not
have to do with the cell cycle, you've
got to have that mutation happen in a lot of different cells
in the same tissue in order for it
to have any significant consequence,
any actual bad effect.
And that's just not going to happen.
And it's the same machinery that defends the same DNA repair
and maintenance machinery that defends against both outcomes.
So essentially, I've called this protagonistic pleiotropy.
I could explain the reason for that terminology if you like.
But the point is that the imperative not
to die of cancer before we've reproduced
has forced evolution to develop DNA repair and maintenance
machinery that's so good, that it's unnecessarily
good for every other purpose.
And so we just don't get any consequences
of mutations of other kinds until much more
than a currently normal lifespan.
Now, that may sound a little abstract and theoretical.
And maybe it's not completely watertight.
So obviously we would like to have data
that actually confirms this.
But that seems to be exactly what we have.
People have done interesting experiments
looking at the rate at which mutations
accumulate in mammals.
And it's looking OK.
During growth, up to adulthood, there
is an accumulation of mutation load in every tissue,
an expectable rate.
But once that animal, mouse, reaches adulthood,
in most tissues, there's nothing.
Any further increase is undetectable.
And of course, if there was no increase, then
there can't be any consequences of an increase.
So that's pretty good.
Now, again, it's not water-tight.
There could be other types of mutation,
or epimutations, changes to the declarations of DNA.
And we've actually spent a bit of money on that question,
trying to actually get a definitive answer
to whether that mattered.
Haven't really got a definitive answer yet.
But insofar as we have an answer at all,
it looks to be coming out the same way.
AUDIENCE: I have a question.
Kind of a bigger-picture question.
So when you're talking about pathology
and not looking at pathologies, cancer,
for example, what's the difference between not
curing cancer but somehow rejuvenating
cells that are spinning?
And so the big vision, is it a top-up rejuvenating preventive
injection once every year or something?
Or is it actually treating pathologies once they occur?
AUBREY DE GREY: Well, a bit of both, really.
So the idea is certainly to identify damage
before it's symptomatic, before it reaches
the point of being bad for you.
So in the case of cancer, that basically
means identifying cells that have got most of the mutations
that you don't want them to have.
And they're dividing when they shouldn't.
And they've escaped the immune system, and so on.
So identifying cells that are aberrant in one way or another.
Actually, our approach for fixing cancer
involves essentially putting a time bomb in there
that stops the cancer from dividing indefinitely.
It eventually causes the end of the chromosomes to get shorter,
so that eventually the cell basically divides itself
into oblivion, by virtue of having the chromosome ends,
essentially, joined together.
But there are other possibilities,
especially enhancing the immune system is
a big fashionable area right now that may very well be
a good answer as well.
So there's various ways to go about it.
But yes.
The idea is to go after the accumulating damage, not
necessarily the pathology itself.
However-- and this is not just really for cancer,
but elsewhere as well--
it may also end up being a good thing to go after them
both together, to go after the damage and the pathology.
I mentioned earlier that the fundamental reason why
the geriatrics approach doesn't work
is because the cause of the pathologies, the damage
is continuing to accumulate.
So what that means is, if you can repair the damage
and stop it from continuing to accumulate,
then maybe some of the pathologies
will just automatically resolve in their own right,
on their own.
But maybe not.
But still, it means that the straightforward geriatric
therapies that go after the pathologies will have
a much better chance against those
pathologies than they would normally have.
Yeah.
Yep, go.
AUDIENCE: Hi.
Since there's quite a good chance
that we'll this technologies work in the near future,
would you recommend any existing methods
to kind of bias more years, to actually reach this point?
AUBREY DE GREY: Yeah, people think I'm
joking when I give this answer.
But the fact is, the only thing you can do
is give me large amounts of money.
[LAUGHTER]
Because the fact is, there's nothing yet, that works.
I mean, of course there are obvious things.
Like, don't smoke.
Don't get seriously overweight.
But nothing new.
No one's come up with anything that
gives more than a very negligible amount at best
of postponement of ill health with what we can do today.
So we're absolutely reliant on still being around in time
for the technologies that don't exist.
AUDIENCE: So I wanted to kind of ask
kind of a speculative question.
Imagine, just a thought experiment,
that these technologies do come to fruition.
We've massively improved human lifespan,
even reaching Longevity Escape Velocity.
How do you see that affecting the evolution
of the human species.
Because some of these methods, where we're introducing
stem cells with modified genes.
Does that become a mechanism of evolution?
AUBREY DE GREY: Right, yeah.
AUDIENCE: What happens?
AUBREY DE GREY: Yeah, that's the answer.
So basically, people say well, oh dear, people
won't have so many kids, therefore,
evolution will slow down.
Complete nonsense.
Actually what's going to happen is the opposite.
Evolution will greatly speed up because a lot
of the technologies that we're going
to be developing that will allow us to implement
these rejuvenation therapies will be ones that
involve manipulating the genomes of people who are already
alive.
So we'll be able to change the genetic composition of people
without any of this terribly time-consuming reproduction
nonsense.
AUDIENCE: You think we'll be able to keep all people
evolving at the same rate?
AUBREY DE GREY: Well, of course, it depends
what you mean by a rate.
Because people will be going in different directions.
Different people will have different modifications.
AUDIENCE: Thinking especially about the things that really
affect success, so like intelligence is probably
the most important trait.
AUBREY DE GREY: Yeah, again, you don't know.
I mean, of course there we've got the issue
that we haven't the faintest idea of what genes actually
really confer intelligence in the first place.
AUDIENCE: Yes.
AUBREY DE GREY: So that's a whole different question.
To be honest, I haven't put much thought into that.
I don't think it's my job.
AUDIENCE: Can you tell me just briefly
about what's being done for telomeric degeneration?
AUBREY DE GREY: Right, so this comes back to the question
that I was asked about cancer a moment ago.
For those of you who don't know, when cells divide,
they ends of the chromosomes, which are called
the telomeres, get shorter.
This is an intrinsic, absolutely irrevocable property
of the way the DNA is replicated.
And in order to compensate for that,
we have an enzyme called telomerase
which sticks non-coding random-- well,
not random, but specifically very simple
sequences of DNA on the ends of chromosomes
to counteract the shortening that would be occurring.
And some people think that it is important for us
to enhance the activity of this enzyme telomerase,
in order to combat aging.
Because cells in older people have obviously
divided more often.
And therefore, they will have shorter telomeres.
The counter to that argument is that actually,
most of our cells don't divide very often at all.
And indeed, not often, even enough, in a normal lifetime,
to get to the point where their telomeres
are problematically short.
And furthermore, that the cells that do divide rather often,
already do express enough of this enzyme,
telomerase, to compensate and make sure
that the telomere only gets shorter at what
seems to be a manageable rate.
However there is still controversy about this.
There are certain reasons to believe
that in some aspects of the body,
especially the immune system, this phenomenon which
was called replicative senescence, with telomeres
getting too short, could be a real thing, a real contributor
to ill health.
So maybe we want to do stimulation of telomerase.
And indeed, there are now massive drugs,
especially that seem to have that effect.
And those drugs are improving all the time.
So that's interesting.
But we always have to be aware that cancer cells divide
when we don't want them to.
And they do it precisely by elevating
their level of synthesis, their level of expression
of telomerase.
So they are cells whose telomerase expression
we would like to suppress.
Now, if we come up with a method for eliminating cancer that
doesn't involve telomere shortening,
let's say, just do that with the immune system,
and works really, really, really well.
Then we're home free.
Absolutely, it will makes sense to look pretty hard at ways
to stimulate telomerase and thereby perhaps rejuvenate
the immune system, and maybe other cell types
that might be experiencing some level
of replicative senescence.
However, it could be that we will end up
wanting to go the other way.
That we will find the suppression
of telomerase activity is the only really solid,
really ironclad way to eliminate cancer.
And that we've just got to live with the side effects,
will actually be worse than what we might see today.
In which, for example, the stem cells of the blood
can no longer divide indefinitely.
And so we end up with anemia, and so on.
The reason why I say we could live with that
is because the way in which we could fix those side effects
is actually conceptually fairly straightforward, namely,
stem-cell therapy.
There's only a very small number of stem cell pools
that are actually dividing often enough for this
to be a problem.
The blood is one, of course.
The epidermus, the outer layer of the skin.
The inner linings of the gut, and probably the lung.
Those are really the only ones that matter.
And so we've been looking at the idea of doing
stem-cell therapies on all of those with cells that
are unable to make telomerase and therefore,
are protected against becoming properly cancerous.
That's the kind of what we think about.
Next?
Who's got the mic.
Yeah, go ahead.
AUDIENCE: I wanted to ask you--
AUDIENCE: Sorry, I had a question.
AUBREY DE GREY: Oh, you had it.
OK.
AUDIENCE: Sorry, this is just maybe a little bit of a sci-fi,
but you are at Google.
Have you thought about your competition
being silicon, IE, we're just going
to upload our consciousness to a computer at some point?
AUBREY DE GREY: Yeah, sure, I'm down with that.
You know, it works, you know, then so much the better.
But at this point, it still looks pretty hard.
I mean, if we do end up being able to develop
really good human-computer interfaces that
allow a really high fidelity training of an external brain
from an internal one, from a natural one and so on,
then we could be talking something realistic.
But the moment, it seems to be a long way off.
AUDIENCE: Hi.
Following up on that, I'm also a huge sci-fi fan.
I was wondering if it's possible to use
your research for long-distance space travel, for NASA?
AUBREY DE GREY: Oh sure, of course.
I mean, the thing about long-distance space travel
is it takes a long time.
And you might not want to be awake all that time.
If your big thing is to go to the stars,
maybe you prefer to be cryopreserved.
And I mean, I'm up for that too.
But yeah, personally, I'm happy down here.
Yeah?
AUDIENCE: So there is a 2015 article in "Cell" magazine,
one of the head researchers is Elizabeth Blackburn,
talking about the shortening of tumor length.
And their observation is that that's not
the driving factor in the rate of aging in yeast cells,
that it's more related to telomerase activity.
You kind of covered this in your answer a couple of times ago,
but does taking that into account
alter your tumor threat or anything?
AUBREY DE GREY: Yeah, not really.
So yeah, Liz Blackburn won the Nobel Prize for this work
on telomerase a long time ago.
She's obviously a very prominent researcher in this area
and she definitely is very interested in the role
that telomerase shortening could have in aging.
Most of what she's actually been able to report
is more at the level of correlation than causation.
You know, for example, that people
who suffer a lot of stress tend to have shorter telomeres.
We don't know which way around it went.
You know, things like that.
But yeah, it doesn't change what I said.
Are we running out of time?
AUDIENCE: Yeah, I have a question about diet.
So basically, earlier you mentioned
that you can use statins to basically reduce
the cholesterol in the blood.
But I believe there is at least two research results that
are quite strong about reducing the incidence
of arteriosclerosis just by changing the diet.
And it does not have the side effects
that statins have, and also decreases,
all kinds of mortality.
So basically, I think what was earlier claimed,
that one cannot change the life expectancy,
currently is not true.
AUBREY DE GREY: Yeah, OK.
AUDIENCE: I'm not saying-- it's not the age-related stuff.
But it's the stuff that's in your third column there,
which can largely be addressed, I believe, with diet.
AUBREY DE GREY: Yeah.
Well, I be very careful with these studies.
So sure, it's clear that atherosclerosis
is disease of Western diet.
It's very much more prevalent now than it used to be.
But if you look at the actual life expectancy aspect,
then it's not very encouraging.
If we just completely eliminated heart attacks and strokes,
then we would only live about five years longer.
If we 100% eliminated them.
And of course, these changes to diet don't, by any means,
100% eliminate them.
So we're still talking a very small amount of difference,
in terms of life expectancy.
Yeah?
All right, thanks very much everybody.
[APPLAUSE]