[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]
