SHANEE NISHRY: Hey, everyone.
Good to have you here.
You may heard of him as the man
who will make you live forever,
or at least until
you get hit by a car.
But here he is, Aubrey de Grey.
AUBREY DE GREY:
Thank you, Shanee.
I like the way that
Shanee introduces me.
It's great.
I've had the good fortune to be
introduced by her twice today.
All right.
So thank you for coming.
I'm going to try and
tell you all about what
we are doing at SENS
Research Foundation.
I have already made
my first mistake,
which to leave the
clicker on my chair.
So as Shanee said, we are
interested in stopping you
from getting sick
as you get old.
It has been a source
of frustration to me
that we get sick as we get
old, for quite some time.
And an even greater
source of frustration
that it isn't a sort of
frustration for everybody.
So I'm trying to change that.
But also, of course, actually
change the facts of the matter,
to try to actually
deliver medicines
that will allow us
to stay healthy.
And so I'm going to spend
the next hour telling you
all about how.
First of all, the success story.
So this is, simply
for illustration,
statistics from the USA
showing the proportion
of the population that are
over the age of 65, which
was way down at 8% or
so in 1950 and it's
projected to be up around 22% in
2050, which is pretty dramatic.
And, of course, this is
a cause for celebration,
because it is the consequence
of a great deal of success
over the past 100 or 150
years in bearing down
on the diseases that
used, historically,
to kill an awful lot
of people in infancy,
or in childbirth, and so on.
And the result is that
pretty much everybody
is surviving long enough to
reach the age of 65 or more.
But it also has, of course,
created some problems.
The economic
problems are perhaps
foremost in many
people's minds right now.
And again, here, I'm just
showing US statistics
for illustration.
But, of course, it's the same
throughout the industrialized
world.
We have this problem that
even though the economy has
been growing nice and fast--
I'm going to use this one,
where you can actually
see my pointer.
I've never understood why these
screens can't made to actually
reflect a laser point of
light, even-- whatever.
So, yes.
So this is the US economy,
the red line going up
at a nice, steady rate.
And if you look at the rate of
medical expenditure in the US
over the same time period, which
is the last 50 years or so,
then it looks perfectly
manageable really.
It doesn't look
particularly scary.
But it's a great
deal scarier if you
take the trouble to divide
one by the other, which
is where the green
line comes from.
And the green line shows
obviously therefore
the proportion of the GDP that
is being spent on medical care.
And it's gone up from
5%, 50 years ago,
to 18%, which is
extremely scary.
And, of course,
is the reason why
we have all these concerns
about pension funds
running out of money,
and Medicare running out
of money, and so on.
So the question is,
first of all, why?
Why have we got this
situation in the first place?
Putting it in starker
terms, why have the diseases
and disabilities of old age,
which, of course, dominant
medical expenditure today, why
have they been so much more
resistant to
medical intervention
than the infectious diseases
that we have more or less
entirely eliminated over
the past century or so?
This is actually
pretty paradoxical
when you think about it.
And in order to
answer this question,
the first thing I
think we need to do
is to ask ourselves
what is aging anyway?
What is the ultimate substrate
for these age-related diseases?
So I'm going to give you
a definition of aging
now, that I'm going to be
using for the rest of the talk.
And this definition
is specifically
geared to trying to eliminate
the distractions that often
come when aging is discussed.
There are many
definitions of aging out
there that really do more harm
than good because they just
confuse the issue.
But this one brings it
down to its essentials.
And I think it's useful.
Essentially, what
I'm trying to do here
is to emphasize that the
aging of living organisms
is really no different
at the bottom line
from aging of inanimate
subjects, like cars,
or airplanes, or whatever.
It is simply a fact of
physics, never mind biology,
that machines with
moving parts do
themselves damage
as a side effect
of their normal operation.
And it's also a fact of physics
that that damage accumulates
and, therefore, eventually
it exceeds the level
that the machine is
set up to tolerate.
So that's true for a car.
It's true for an airplane.
And it's true for a human being.
It's true for the human body.
The human body does a lot
of different types of damage
to itself, which I'll be getting
onto over the next while.
And, therefore, we are
subject to a whole bunch
of different eventual
failure modes,
so to speak, of the body.
And that's really
all it's about.
So really what that
means is that we
must address a very
fundamental misconception that
is prevalent within
society today concerning
the diseases of old
age on which we spend
so much money, diseases
like Alzheimer's, and most
cancers, and
cardiovascular disease,
and type 2 diabetes, and
osteoarthritis, and so on,
and so forth.
These diseases are normally
viewed as diseases.
In other words, they're
viewed as, in some sense,
similar to infections,
and potentially amenable
to the same kind of
medical interventions
that infections are amenable to.
But they're not.
They're actually
all part and parcel
of one single process,
the accumulation of damage
that the body does to
itself in the course
of its normal operation.
So not only are
they, as we all know,
widespread and staggeringly
costly, but they are universal.
The only way that you will
not get a particular disease
of aging is if you die
beforehand of something else.
You are going to get it.
And furthermore, they
not medically curable
in the strict sense
of the word "curable."
What do I mean by
the strict sense?
I simply mean that we cannot
eliminate them from the body
in the way that we can
eliminate an infection.
If you eliminate an
infection, then the person
isn't going to suffer
from that infection
again unless they
get reinfected.
But you can't do
that with things
that are a side effect of
being alive in the first place,
other than by eliminating being
alive in the first place, which
would kind of defeat the object.
So let's not do that.
But that does not
necessarily mean
that we can't address
the diseases of old age
using medicine.
It just means that we have
to rethink our starting point
in designing the medical
interventions that we
might be use.
I'd like to put it this
way, even more starkly.
Most people think of
the various causes
of ill health along the lines
that I'm showing in this table.
There are various
types of disease.
There's infections,
communicable diseases.
And there are
congenital diseases
that a small
proportion of us have
because we got dodgy DNA
of one sort or another one.
And then there are the
chronic age-related diseases,
which are the subject of
so much concern and so much
expenditure today.
And then, in most
people's minds,
there is this completely
separate category
called aging itself,
which is composed
of these nonspecific, rather
poorly defined things,
like sarcopenia, which
is the decline of muscle
mass in the elderly;
or a gain of fat mass;
or a decline in function of
the immune system, these things
that we don't really
think of diseases.
That's what most people
have in their minds when
it comes to ill health.
But it's nonsense.
This is the way that we ought to
be thinking about all of this.
All the columns
are the same here.
It's just where the black
line is that's changed.
There are diseases and
then there's aging.
But the diseases of old
age are part of aging.
The only difference between
column three and column four
here is that column
three consists
of those aspects of aging
that we have taken the trouble
to give disease-like names to.
Its purely semantic and no more.
That is an absolutely
fundamental thing
that I'm going to be leaning
on for the rest of the talk.
So I wanted to make sure
you have it in your heads
very clearly at the outset.
Now, what does this
mean in economic terms?
I mean we can look at it in many
terms, humanitarian of course.
But let's just do it
in terms of economics.
And here, for the
moment, I'm going
to move away from medical
expenditure to the expenditure
on medical research
because, unfortunately, it's
the same story, perhaps
in even starker terms.
And again, I'm going to
use US statistics just
for illustration, because
I happen to have them.
But again, this is
absolutely the same
across the industrialized world.
So the NIH, the National
Institute of Health,
is the counterpart of
the Medical Research
Council in the UK.
It's the government body that
is responsible for essentially
all public expenditure
on medical research.
And it has a nice healthy
budget of $30 billion a year.
But only 3% of that
budget is spent
on aging, the National
Institute on Aging.
That is pretty bad
news given that
the vast majority of
medical expenditure
and, of course, suffering
caused by disease
and so on, in the US,
is driven by aging.
It doesn't make sense.
But that's how it is.
That's bad.
But it's not nearly
as bad as it gets.
Even within the National
Institute on Aging,
only about one sixth of that
budget, that $1 billion,
is spent on understanding
the biology of aging.
The rest goes on specific
research on Alzheimer's disease
and/or geriatric medicine,
or even social gerontology,
studying how to preserve the
dignity of the elderly, things
like that.
Which is all very well.
They're important stuff.
But it's not what would actually
give the bang for the buck.
So it's a disgrace
that it's so small.
And that's not the
end of the story.
The fact is that even
within the Division
of Aging Biology of
the NIA, of the NIH,
the amount that's actually spent
on doing something about aging
is way under the 10%.
That number, $10
million, I've got there,
is a very generous estimate.
Really, that's amazing.
Most gerontology consists of--
it's a bit like seismology.
People who study
earthquakes, they
understand that what they
study is bad for you,
but they're not proposing to
actually do anything about it.
It's all about just getting
out of the way really.
So it's a bit sad.
I mean to put it in real
perspective, what we're talking
about here is that my little
foundation, the SENS Research
Foundation that's been created
around my work, which has only
existed for a few
years, and we only
have a budge of $4
or $5 million a year,
it's on the same order
as the US government.
That is fairly shocking.
So something better
be done really.
And that's why I go around the
world giving talks like this.
This is essentially
where we are today.
If you look at the bottom of
this diagram, what I'm saying
is what I told you already.
Metabolism causes
damage, causes pathology.
In other words, the
network of processes
that keep us alive from
one day to the next,
which is what biologists
call metabolism,
causes various types of
molecular and cellular change
to the composition and
structure of the body, which
I'm calling damage.
And that damage accumulates.
And eventually, when it
exceeds a certain threshold,
it impacts the
function of the body.
And that's when the diseases
and disabilities of old age
begin to emerge and to progress.
And all of what
we try to do today
to attenuate and alleviate
the pathologies of old age
consists of what I'm calling
here the geriatrics approach,
geriatric medicine.
It means, in a nutshell,
completely ignoring everything
that I've told you in
the last five minutes.
It means pretending that
the diseases of old age
are just like infections and
can be eliminated from the body.
It's obviously
complete nonsense.
First of all, for the
reason I've told you,
namely the damage, it's
continuing to accumulate.
So obviously,
anything that comes
under the geriatrics
heading is going
to become progressively less
effective as time goes on
and as the damage becomes
more and more irresistible.
And secondly, because the
pathologies of old age
are quite numerous.
You're not supposed to be
able to read this slide.
Don't worry.
This is simply a nice selection
of the things that go wrong
with us as we get older and
that we would rather didn't.
So it's completely hopeless.
But we spent a spectacular
amount of money on it.
Now, I am by no means the
first person to point this out.
For the past 100 years, there
have been a few people out
there trying to get people to
understand that actually if we
want to do anything
about aging, we
have to intervene at an earlier
stage in the chain of events,
in the chain of events
that I've just shown you.
And that's what has given
rise to what I'm calling here
the gerontology approach,
which is the approach favored
and pursued by that rare
breed of people who study
the biology of aging with a
view to actually doing something
about it in due course.
However, that approach
has also failed completely
to deliver any kind
of actual impact
on the ill health of old age.
Why should it be?
Well, what is the
gerontology approach?
It consists of essentially
trying to clean up metabolism,
trying to slow down the
rate at which metabolism
creates damage.
And that sounds
like a great idea.
Because certainly
if we could do that,
it would postpone the age
at which the damage reaches
a pathogenic quantity.
But there's a couple of problems
with the gerontology approach
too.
The first problem is that
it's only slowing down
the accumulation of damage.
So that means that the
later you start the therapy,
the less benefit
you're going to see.
The less time you're
going to have to extend,
before the pathogenic
threshold is reached.
And that's a bit of a
shame because some of us
may already have the misfortune
to be in middle age or older
by the time that the therapies
in question are even developed.
So that's a bit of a shame.
But worse than that,
the gerontology approach
suffers a problem that is rather
analogous to this problem,
namely-- there we
go-- this problem.
Metabolism is
rather complicated.
This is a simplified
diagram of a small subset
of what we know about how
metabolism really works,
about how the body works.
And as you can see,
it's a bit hairy.
And as engineers, or as people
who work with engineers,
I'm sure you will understand
that it's pretty implausible
that we would be
able to, in some way,
tweak this vast network
of uncommented spaghetti
code in a manner that would
stop it from doing the thing we
don't want it to do,
namely creating damage,
without also stopping
it from doing stuff
that we do want it to do,
like keeping us alive.
So it's a waste of time really.
There's no way in
the world that we're
going to actually
make this work.
But if that the end of my story,
I wouldn't be standing here.
You knew that.
So what's the "get out?"
How do we extract
ourselves from this?
Well, ultimately what we do
is we go back to the analogy
that I started with
some minutes ago.
This car is more
than 100 years old.
And, of course, there
aren't many cars like this.
But they're not all that rare.
The point I want to
highlight about this car
is that it was not
designed to last 100 years.
It was designed to last maybe
10 or 15 years before it would
fall apart and you
go and get a new one.
And the reason it's lasted
so long is understood.
We all know that the way that
enthusiasts allow their cars
to live a long time is by
doing really comprehensive
preventative
maintenance on them,
by simply repairing the
damage that the cause does
to itself as a side effect of
its normal operation, a phrase
that you may recognize
from a few minutes ago.
Now, that means that
we can realistically
ask ourselves, well,
maybe we could actually
do the same thing
to the human body.
Maybe we could engage in
preventative maintenance.
And if it was sufficiently
comprehensive,
maybe it would have
the same effect.
It would greatly extend
the healthy longevity
of the machine that we call the
human body beyond the longevity
that it was initially set
up to be able to achieve.
This is what that means in terms
of comparing and contrasting
with the other approaches.
Rather than trying to slow down
the rate at which metabolism
creates damage, as the
gerontology approach tries
to do, or indeed the rate at
which damage creates pathology,
as the geriatrics
approach tries to do,
instead the proposal is to
uncouple those two processes
from each other.
To actually go in and
periodically repair the damage
so that the damage, even though
it's still being created,
never actually reaches
the pathogenic threshold.
What I'm going to be trying
to persuade you of today,
in the rest of the talk, is that
this approach is very much more
favorable than the other two.
That we have a realistic
chance of pulling it off
within the foreseeable future.
So in order to go
on to that, I'm
going to now start talking
about actual biology.
I'm not going to get too
technical, obviously.
But I'm going to try to give
you a feel for what this is all
about.
The first thing we
have to do is to define
the problem in concrete terms,
in down-to-earth, actual
biological terms.
And that is what
this table does.
Here we have a
list of seven types
of damage, seven
categories of damage.
And as you can see,
each of these things
is a genuine, bona fide,
physical, biological thing.
Cell loss simply means
cells dying and not
being automatically
replaced by the division
of other cells, a
very simple concept.
And this is a
classification which
I have been using for this
purpose for quite some time.
Now, you may have a
couple of questions
about this classification.
And I want to answer
them right at the outset.
The first question you may
have is, well, hang on,
what's so useful about
this classification?
You recognize, as I've
already, in fact, highlighted,
that there's an
awful lot of things
that happen during aging.
There are, indeed, an awful lot
of different types of damage
that gone on.
So a thousand things can be
classified, can be grouped,
into seven different categories
in many different ways.
What's so useful about this
one, you may be asking yourself?
The answer is that within
each of these categories
there is a particular generic
type of intervention that
exemplifies, that illustrates,
the maintenance approach.
That within each category
there may many examples.
But all of them can be,
in principle anyway,
addressed by, broadly
speaking, the same therapy,
differing only in details
from one example to another.
That's the absolutely
fundamental thing
that you're looking for in
any kind of classification
of a problem into subproblems.
So that's what this
classification is all about.
The second question you
may have is, well, hang on,
how do we know that
this is exhaustive?
How do we know that there
isn't an eighth category
and a ninth one?
And, of course, we
can't absolutely know.
But the good news
is that we have
at least a good circumstantial
argument that it probably
is an exhaustive classification.
What is that
circumstantial argument?
Here it is.
It's been the same
classification
for more than 30 years.
All of these things
have been major topics
of research and discussion
within gerontology
since at least the early 1980s.
Now, one could say, well, that's
not really a fair argument
because people
weren't really looking
to classify damage in
this way back then.
And that's kind of true.
But it's increasingly
not true because the fact
is I've been out there,
making a nuisance of myself
and challenging
people to actually
come up with other
categories to add
to this list for more
than a decade now.
And I do seem to be
getting away with it.
I am like, you know,
getting away with it.
So that's pretty good news.
I mean it's a
circumstantial argument.
But it's quite
compelling really.
Now, I'm going to spend a
few minutes now highlighting
the relationship between
damage and pathology.
And this is really important
because ultimately it's
where the rubber hits the road.
At the end of the day, we need
to actually convince ourselves
that if we could repair all
of these types of damage,
we genuinely would
have this effect
on the various
pathologies of old age.
What I want to
emphasize to you here
is that the relationship
between damage and pathology
is, in some cases, quite
complex, but it is established.
It is well known.
The stuff I'm
going to be talking
about in this
particular section,
for the next couple of minutes,
is not innovative ideas
without portfolio, that
SENS Research Foundation
has put forward.
These are things that no
one working in these field
would dispute.
So let's start with cancer.
Cancer is the simplest example.
Because in this case, it's
pretty much a one to one
relationship between the
pathology and the damage.
There's this one
category of damage
that I define as
division-obsessed cells,
in other words, having too many
cells because there are cells
which are dividing when
they're not supposed to.
That's pretty much the
definition of cancer.
So it's a nice,
straightforward one to one
relationship between
a type of damage
and a type of
age-related disease.
But, in general, it's
not quite like that.
So the heart is a good example.
The heart is an
organ that can go
wrong in a whole bunch of
different ways in old age.
And it turns out that the
different ways it can go wrong
are driven by different
types of damage.
So let's first of all
take atherosclerosis,
the accumulation
of fatty deposits
in the major arteries,
which leads, of course,
to heart attacks and
strokes, and therefore
to the major killers,
the number one
killer of the Western world.
That comes down, at the end of
the day, to this thing here,
I'm calling intracellular
junk, molecular garbage
that accumulates within cells.
In particular, what
happens here is
that there are a type
of white blood cell,
called a macrophage,
which goes into the artery
wall for the purpose of
clearing up detritus.
And it's very good at it.
But the macrophage gets
poisoned by contaminants
in that detritus,
which eventually
cause it to become more of
a problem than a solution.
And I will come back
to that at some length
later on because we've done
some quite important work
in addressing that over
the past few years.
The second type of way
that the heart can go wrong
during old age is
arteriosclerosis,
which is the stiffening
of the major arteries.
This is something that is very
important in terms of pathology
because it leads to increased
blood pressure in the elderly,
and therefore to things
like kidney failure.
And the ultimate molecular
driver of arteriosclerosis
is this thing at the bottom,
in pink, the stiffening
of this lattice of proteins
called the extracellular
matrix, which essentially
gives each of our organs
their shape and physical
properties that it has.
And, in particular, the
extracellular matrix
of the major arteries is
extremely essential in terms
of giving them the
elasticity that they
need to dampen the pulsation of
the heart, of the heart beat,
and thereby protect the more
fragile capillaries and smaller
parts of the circulation
from the blood pressure.
So that's arteriosclerosis.
The extracellular
matrix becomes less
elastic as a result of
chemical modifications.
And we need to fix that.
Then there's amyloidosis,
which actually
has been discovered
quite recently
to be a major killer
of the really elderly.
People who live more
than 105, 110, it
turns out that most of them,
certainly half of them,
die of a disease called senile
cardiac amyloidosis, which
is essentially the accumulation
of molecular garbage
outside the cell, that
thing I wrote in blue here.
That's all about
a type of protein
that gets into this kind
of fibers that essentially
weaken the joints between
the various muscle cells that
make the heart up and
weaken its ability to beat.
So that's rather bad for
you, eventually, of course.
And then finally
there is cell loss.
The heart actually does
not beat on its own.
It only beats when
the brain tells it to.
And the cells in the heart
that mediate that signal,
they're called pacemaker cells.
And it turns out that they
don't maintain their numbers
during age.
They die progressively.
And eventually, you
haven't got enough of them
and the heart stops
listening to the brain.
And it just doesn't
beat anymore.
So that's another way
that the heart can stop.
So, as you can see,
the relationship here,
between damage and this
particular type of pathology,
is quite a complicated
one, a many to one
relationship for sure.
But, like I said earlier,
it's really well understood.
And that's the important
thing I want to get across.
The same with
Alzheimer's disease.
Alzheimer's disease was defined
about 100 years ago or more,
as the combination
of these two things
here, a type of
junk inside neurons
called tangles and another
type outside called plaques.
And now, of course, we
also know that there's
a lot of cell death in
Alzheimer's disease.
So again, a complex
relationship, but a well
understood one.
The big thing to take into
account here and to emphasize
is that these
nonspecific aspects
of aging, that we don't give
disease-like names to, the same
applies.
Most of these things--
pretty much everything
except division-obsessed
cells-- ultimately
can be linked causally to
various types of decline
in function, like
loss of muscle,
or loss of immune
function, and such like.
So this is really good news.
We have a very clear
idea of this linkage.
All right then, enough
about the problem.
Let's go to the solution.
So what is the preventative
maintenance approach?
It falls into these
four types of approach,
replace stuff
that's gone missing;
remove stuff that
has accumulated,
that you don't want;
sometimes in situ repair
of stuff that you don't want
to remove or to replace;
and sometimes reinforcement.
That means essentially breaking
the link between damage
and pathology, somehow
doing something to the body.
That means that the damage
can still accumulate,
but it no longer actually
has any pathogenic effects.
And when we come down to
specifics, it's all about this.
So I won't go through
this in detail.
I'm going to touch on a
couple of the examples
here in a moment, to look at
the details of the pathologies.
But essentially what
I'm showing here
is that we know exactly how
to do this in principal.
Some of this, much
more than in principle.
Lets take cell loss.
The main way-- the generic way
to restore cellularity, cell
number, to a given tissue is,
of course, stem cell therapy.
That's true for cell
loss during aging,
just as it is in terms of
any kind of acute trauma
or injury for which stem
cell therapy may originally
have been developed.
Parkinson's disease is
a great example of this.
It's a disease in which
cells in one particular part
of the brain die
unusually rapidly.
And stem cell therapies
for Parkinson's, they
were first attempted
nearly 20 years ago,
when we really didn't know what
we were doing with stem cells.
But even then, they sometimes
worked really, really well.
And now, there's a
great deal of resurgence
of interest in this and new
clinical trials going on.
And I think there's quite a
good chance, at least 50%,
that within as little
as 10 years from now,
we will be able to say that
Parkinson's disease has
been cured.
So I won't go on to the
others now because I'm
going to touch on some
of them in detail.
What I'm going to do
is talk about how far
advanced they are.
And I'm going to start with the
ones that are most advanced.
So I'll just mention clinical
trials for stem cell therapy.
These are already in
progress, in certain cases.
And that's great.
That's wonderful.
And actually, it's
the main reason
why SENS Research Foundation
doesn't do anything
to speak of, hardly
anything, in the whole area,
because our contribution
would be a drop in the ocean.
Another case that
I want to highlight
in a little more detail
consists of this business
of molecular garbage outside
the cell, which in general comes
down to this thing
called amyloid.
Amyloid, as I mentioned earlier,
accumulates in the heart and it
also accumulates in the
brain during Alzheimer's.
That's what female plaques are.
And 15 years ago, or so, it was
determined, at least in mice,
that one could get rid of this
stuff just by immunization.
Essentially, one could
trigger the immune system
to engulf the material,
get it inside the cell,
inside phagocytic cells.
And this was enough to get
rid of it, to remove it,
because the machinery
for breaking things down
inside the cell is
much more powerful
than what exists outside.
And this moved, in the case
of Alzheimer's disease,
very rapidly to clinical trials.
And those clinical
trials got to phase III
and reported just a year ago.
And the reaction
was frustrating.
The trials did not achieve
their clinical endpoints.
That isn't what was frustrating.
I would have been
absolutely amazed
if people, given these
treatments to get rid
of plaques, had
actually exhibited
any significant restoration
of cognitive function.
Why?
Because it's not the whole
of Alzheimer's, dummy.
I mean Alzheimer's is these
three things that happen.
It's not just
amyloid accumulating.
It's also tangles accumulating
inside the cell, which
was not targeted by the therapy.
And so there was
no reason why we
would expect them to go away.
And similarly,
the cells that had
gone missing, that had died,
were not being replaced.
There's no clear
chain of causation.
It's not as if we
already had any reason
to believe that if
you remove plaques
then the tangles would
go away on their own
or the cells would
somehow regenerate.
I think it's a bit like what
I'm saying at the bottom there.
It's a bit like saying let's
take a car apart and put
the individual
components out in a line.
And then let's pour
burning petrol over them
and we'll expect to see
some kind of motion.
It wouldn't happen really.
So it's frustrating that medical
researchers and scientists
are often rather careless
in their evaluation of how
technology is supposed to work,
especially divide and conquer
technology of this kind.
Let me talk about another case.
And here I'm going to emphasize
the role of the private sector
and especially the role
called of venture capital.
Because obviously
in the IT world,
you guys are quite
tuned into all of that.
And you may be
wondering already why
does a nonprofit, such as
SENS Research Foundation,
really need to exist, if
all of this is so clear?
So I'm going to
talk about this case
because it's an
interesting, kind
of intermediate,
transitional case.
It concerns
death-resistant cells,
which is a category
that I've defined,
that simply means "the other
way of having too many cells."
You can have too many
cells because cells
are dividing when
they're not supposed to.
That's what cancer is, as
I mentioned a moment ago.
Or you can have too many
cells because cells are not
dying when they are supposed to.
People often overlook that
because they think, well, cells
are not supposed to die, right?
But that's not true.
It turns out of there
are certain parts
of the body in which
cells are absolutely
required to die in order for
the whole system to function.
So we'd like to be able to
get rid of these things.
And for a long
time now, I've been
saying that the way to
do this is with something
called suicide
gene therapy, where
you use engineered
viruses to introduce
a toxic gene into cells.
This gene creates a protein that
will actually kill the cell.
And the way you do it is by
ensuring that the protein is
only synthesized
within the cell,
in the case where the cell has
got into this bad state, where
you'd like to get rid of it.
So this is something that
is routine in the lab,
in mouse experiments.
But it's very
dangerous and so it
hasn't got to prime
time for the clinic yet.
But it will.
It will.
So that was the thing I was
interested in making happen.
And the good news is that
a couple of years ago,
a group at a very prestigious
institution called the Mayo
Clinic, actually had a
go at pretty much that.
What they did was, since
they were working in mice,
they didn't actually need to
resort to this engineered virus
business of suicide
gene therapy.
They just introduced the
suicide gene transgenetically
so that it was in
every cell in the mouse
from the time the
mouse was conceived.
And what they did was they made
a combination of two things.
First of all, they
introduced a second mutation
into these mice, a
different mutation,
which caused these
death-resistant cells
to accumulate much,
much more rapidly
than they normally would.
But which did not
cause any other aspect
of aging to be accelerated.
So these mice basically died of
having too many death-resistant
cells.
And they died pretty quickly.
They died at less than
half the normal age.
This mouse at the bottom
here is such a mouse.
It's less than a year old.
And it's only got about a
month to live, if it's lucky.
And you can see, it's
very unhealthy already.
So what they did was,
this research group,
they engineered this suicide
gene into these mice.
And they engineered this in what
we call a drug inducible way.
In other words, in such
a manner that they could
activate that gene,
but only, of course,
in the cells that
they wanted to kill,
by giving the mice some simple
drug in their drinking water.
Until that time,
even the bad cells
would not actually die
because they would not
express the suicide gene.
So what they did was they
waited until, let's say, halfway
through these mice's lifespan
before giving them the drug
and activating the suicide
gene, so that a whole bunch
of these cells would
already be in existence.
And the result was very nice.
The top mouse there
is one like that,
same age as the bottom one.
And as you can see,
it's perfectly healthy,
doing very fine.
And they measured the
relative health of these mice
in all manner of different ways.
This graph on the right is
just one of the dozen things
they did.
It's to do with muscle mass.
So this was all very good news.
Now, here's the
interesting thing.
They did this in an
academic institution.
But they decided to go out
and start a startup company.
And they got VC money
really pretty fast.
Why is that interesting?
The reason it's interesting
is because the experiment
was extraordinary preliminary.
First of all, it was in mice.
And we all know that
stuff that's in mice often
takes quite a long time to
translate to the clinic.
Second of all, they were working
in this artificial system
where they had accelerated
one aspect of aging very, very
dramatically.
So there's no evidence from
this experiment showing
that the senescent cells,
these death-resistant cells,
are actually all that bad
for you in a normal mouse,
in a normal lifespan.
So this was really a
bit of a leap of faith.
The third thing that
was very preliminary
about this experiment was that
it was a transgenic experiment,
where they introduced this gene
into the mice that allowed them
to kill the relevant cells
at a point of their choosing.
Now, tells us absolutely
nothing about what
the actual plausibility is
of the company's business
plan, which is to create
an actual pharmaceutical,
a small molecule drug that
would do the same thing.
There's absolutely
no way that there's
any evidence from
this experiment
that that is even possible.
And the fourth thing is that
even if you forget all this
and you just presume investors
were stupid or at least
they thought that their eventual
customers would be stupid,
that they might be going
for some kind of very
superficial bottom line, that
bottom line would be longevity.
There's one thing I haven't
told you about this experiment
so far.
You probably think that
these mice at the top, right,
probably lived a normal
life, like 2 and 1/2 years,
as it gained certainly a year
for the mouse at the bottom.
That turns out not to be true.
It's actually the case
that the mice at the top
died after a year, same
as the mice at the bottom.
Because it turned out
that was something else
than the gene did,
that the mutation did,
that caused the
accelerated accumulation
of death-resistant
cells, that was not
to do with
death-resistant cells.
It just basically
made the heart unhappy
and so they died anyway.
So on every single measure
that you could think of,
this is a massively
preliminary experiment.
But they got their money.
How did they do it?
I think that the answer is
a very encouraging answer.
Namely, that investors,
smart investors,
who are looking at things to
do with the eventual delivery
and development of anti-aging
medicine that actually works,
have been paying
attention to the numbers.
They've started paying
attention to the fact
that the real anti-aging
industry to come,
the anti-aging industry
consisting of therapies that
work, is going to be
the biggest industry
ever, by a very large margin.
It's going to be the
industry of all time.
So that, of course,
means that if you
want to get into it, if
you want make money, then
your calculations of decisions
about whether to go for it
or not will use
different numbers.
You will be willing
to accept higher risk.
You will be willing to
accept a longer time-frame
before access, all those things.
That seems to be happening now.
That's why this kind of
thing is actually occurring.
And it's very
heartening, indeed.
All right.
So you may think,
well, OK, that's great.
So even something
really preliminary
is getting funded by
the private sector.
Why does SENS
Research Foundation
need to exist as a nonprofit,
funded by philanthropy?
Well, I'm afraid the
answer is that even
though some things are moving
forward nicely like this,
and they are in the position
also being able to get money
out of venture capital, a lot
of things that need to be done
are still at an earlier
stage than that.
At early enough
that I don't think
the calculations are
going to fly for a while.
The mission statement of
SENS Research Foundation
is that we want to create a
rejuvenation biotechnology
industry.
Don't get me wrong.
We definitely want
that to happen.
But there are some things where
it's not ready for prime time
yet in the private sector.
And I'm going to give you
an example here because it's
a good example of the stuff
that we've been doing.
It's showing very
good proof of concept.
But it still has a
little way to go.
And it's do with this
thing, molecular garbage
inside the cell.
And it comes back to
the number one killer
in the Western world,
atherosclerosis.
Atherosclerosis, as
I mentioned earlier,
starts with white blood
cells, a particular type
of white blood cell called
a macrophage-- excuse
me-- going into the artery
wall and clearing up garbage,
clearing up detritus.
And it's very good at it.
It basically recycles
various materials
and exports them
back out for reuse.
But there are
certain contaminants
in that detritus which
the macrophage is not
equipped to handle.
And those contaminants
poison the macrophage.
And eventually, it doesn't work.
The particular part of the
macrophages that stops working
is this thing called
the lysosome, which
is kind of the garbage
disposal machinery of the cell.
And it's really
an important part.
So when the lysosome
stops working,
the cell stops being
able to do things
that it used to be able to do.
And eventually it
turns into this kind
of undead thing called
a foam cell, which
is what we have showing here.
This is the first visible
stage in atherosclerosis.
And actually, all of
us have foam cells
in our major arteries,
even as young kids.
But we don't have
very many of them.
And when we don't have very
many of them, lo and behold,
they're not harmful.
But eventually there's too many.
And the environment,
the other cells around,
start to get a little angry.
They get inflamed and bad
things start happening.
More white blood cells
pile in, in an attempt
to solve the problem.
But they got poisoned
as well, so they
become part of the problem.
And the plaque grows and grows.
And eventually you end up
with the plaque bursting.
And that's when you got
heart attacks and strokes.
So what could we do about this?
Well, about 15
years ago I proposed
that what we really need to
do to stop this kind of thing
happening-- and a
similar kind of thing
happens with different toxic
molecules in, for example,
macular degeneration,
the number one
cause of blindness
in the elderly.
The thing we need
to do is simply
equip the relevant cells
that are being poisoned
with additional machinery
for breaking things down.
So that, in particular,
they can break down
the things that
are poisoning them.
And it turns out that that's
not so hard as all that.
In the case of
atherosclerosis, there
is just one particular compound.
It's called
7-Ketocholesterol, which
appears to be responsible for
at least most of the problem.
It's not by any
means the only thing
that accumulates in
macrophages over time.
But it does seem to
be the most important
in terms of its abundance
and its toxicity.
And what we decided to
do was to take a leaf out
of the book of environmental
decontamination, not even
a biomedical field at all.
So, of course, no one
working in gerontology
knew anything about this.
But what we did was we
simply used the idea
that you might be able to find
bacteria in the environment,
in the soil, that could
break down the material that
is poisoning these
macrophages, this compound
7-Ketocholesterol.
Now our idea was not,
I should emphasize,
that having found
such bacteria, we
would inject them into the body.
I have to think that
might have side effects.
But what we decided
to do instead
was, once we found
such bacteria,
we would identify the genetic
basis for that capability,
the genes and enzymes
that they had,
that allowed them to break
down these compounds.
And then we would introduce
those genes and enzymes
into human cells,
thereby augmenting
the capacity of those
cells to break things down.
So here's the first step.
And as you can see, this
paper came out in 2008.
It was actually the
first paper that
was published out of
work funded by us.
And it went very nicely.
We found bacteria
that did the job.
What you're seeing
here is what's
called an enrichment
culture, where
we take a whole bunch of
different bacterial strains
and we give them this
stuff, 7-Ketocholesterol.
And we don't give them
anything else to live on.
The idea here is that if
they can break down 7KC,
then they can grow because they
can extract energy from it.
And if they can't, they can't.
So most of these strains can't.
They just there like lemons,
doing exactly nothing.
But a couple of them
are doing very fine.
You've got a couple of strains
there which after only 10 days,
have consumed the
entire material.
So that's great.
Then we're got to, as I say,
find the genes and enzymes
that they're using.
And that turned out
not to be too hard.
This is one way
the way we did it.
It's called mass spectrometry.
We essentially identified
the breakdown products
that the bacteria are creating
in the process of breaking down
the original substance.
And that allows us to infer what
enzymatic reaction is occurring
and used by informatics to
identify candidate genes.
There are other approaches.
We also used expression
analysis to find
which genes were being activated
when we gave them the 7KC,
and so on.
All these methods seemed
to work pretty well.
The long and short of it
was we had a few candidate
genes by about 2010.
That's when things
started getting tricky.
Step three in this
process is the hard one,
which is to actually get
these enzymes to work
in a human cell.
The reason that's hard
is because humans cells
are very different
from bacteria.
Bacteria doesn't
even have lysosomes.
But we managed it.
First of all, we actually
had to do the localization.
We have to get our enzymes
to go to the lysosome.
And this shows that
we could do that.
The red on the left is a stain
for the lysosome in cells.
The middle one is our
engineered protein.
And the fact that they're
overlapping reasonably well
shows us that
plenty of our enzyme
is going to the right place.
So that's all good.
But at the end of
the day, we also
had to show that it worked.
And that was what we were able
to show maybe 18 months ago.
This graph is a
summary of the results.
Essentially what it says
is that if you give cells
a completely insupportable
amount of 7KC,
on the right-hand
end here, then it
doesn't matter what you've
done to them in terms
of giving them extra enzymes.
They die anyway.
But if you give them a
relatively modest amount
of this toxic
molecule, then the fact
that the right-hand bar
of each of these groups
is higher than the other
bars, that basically says
that the cells which
have the enzyme
seem to be targeted to the
right part of the cell,
the lysosomes are projected.
They survive better than other
negative control cells, cells
that don't have an enzyme, or
they have the wrong enzyme,
or they have the enzyme not
targeted to the right place.
So this is a extremely
good proof of concept.
We're very happy about it.
We have a couple
more steps to go
before we think we would
be able to take this
to the private sector.
First of all, we
would need to get
this working in a
different cell type.
We did this in
fibroblasts, which
happened to be
easy to work with.
But we need to get it
to work in macrophages.
Then we need to
move to mouse models
of cardiovascular
disease and show
that it's protective
there as well.
But we're well on our way.
I think I can probably trust you
to understand that this really
is a very effective
proof of concept.
And we learned a lot more.
We only have $4 million
a year, or thereabouts.
But we are spending
it very efficiently.
We have a headquarters in
Mountain View, California,
just a couple of miles
from the Googleplex,
that has a few thousand square
feet of lab space, where
we do three of our
major projects.
And we have more than
a dozen other project
at various universities
around the world.
That one I just
described to you happens
at Rice University in Houston.
We also have an educational
arm, which I always
like to mention
because I think it's
very important to understand
that we're trying to grow
the next generation of
rejuvenation biotechnologists.
So that's something
that you can read
about at the website, of course.
Now, I thought I should mention
a little bit about credibility.
Because maybe 10 years
ago-- some of you
have already come across
me-- it was actually
pretty tough to
sell this concept.
I think you already got the
idea from my early remarks
that the whole
maintenance approach is
a big departure from what people
had previously been thinking.
People who were
working in gerontology
viewed this whole idea of damage
repair as a complete solution,
as a very, very
implausible idea.
It was as far away from
the historical thinking
as the geriatric
medicine approach was.
So I had to do a
lot of education.
And it took a while.
But the good news is that it
really has been very effective.
We are now in the very
heartening position
of having this kind of research
advisory board, of very
obviously explicit
endorsers of our approach.
Every single one of these people
are really, really prestigious
dignitaries in their various
biological disciplines.
Now, there are obviously
still a few people out there
who just refuse to be
educated about this.
But by and large, the
credibility barrier
has been breached, which
is very nice to know.
But still, we're got to do more.
One thing we have to do,
of course, is publish.
We have to demonstrate
the validity of what we're
doing in the traditional manner.
And that's, of course,
what we're doing.
So these are just a small
selection of the papers
that we've published recently.
That one at the top is the one
I've just mentioned, of course,
the rescue of cells
from 7-Ketocholesterol.
But we've done a
lot more than that.
A couple months ago,
we had a lovely paper
in a very prestigious journal,
"The Journal of Biological
Chemistry," showing
that we could address
senile cardiac amyloidosis
using antibodies
that would break the stuff down.
A couple of other
examples there.
So things are going nicely.
But, of course, there's
still a very long way to go.
I'm pretty much done.
And I'm just going to spend a
few minutes on other matters.
The first thing I'm
going to tell you
is what I'm not
going to tell you.
In other words,
I don't really do
the sociological considerations.
I do have to.
Some of you probably know that
I do a brutal amount of media.
I do probably 100
interviews a year.
And the bulk of my time
in those interviews
is spend answering questions
along the lines of, oh, dear,
where are we going to
put all the people,
or won't dictators live forever,
or won't we all get bored?
Shall we say, I have
become a little bit
bored myself of these questions.
I regard them as being
ultimately founded
on a degree of
myopia with regard
to the importance of this
work, a degree of ability
to put out of one's mind
the fact that we have
quite a bad problem
today with aging,
namely a problem of 100,000
people every single day
dying of it.
That's 2/3 of all deaths.
In the developed
world, it's something
like 90% of all deaths.
And, of course, it's
not just the death.
It's also all the
suffering that most people
have for a long period of
time before they die of aging.
So it's fairly obvious that
this is not really the right way
to think about it.
We shouldn't be thinking
about these problems.
We should be thinking about
this, that if we were actually
to move to a
post-aging world, we
would have no
age-related ill health.
People's health would
not be a function
of how long ago they were born.
The elderly would still be
contributing wealth to society,
so these therapies would
pay for themselves.
The elderly would not be a
burden on their kids anymore.
This is obviously something
that a lot of the elderly
worry about a great deal.
So that's kind of
the way I think.
All right then, so the
final point, call to action.
What can you guys do?
As far as I'm concerned,
this is really
where I want to place
emphasis because whenever
I give a talk like
this, or an interview,
I feel I do get people inside.
I do get people to
understand that, yes, this
is a really important
problem, and yes, we
do have a respectable
chance to actually solve it.
But I need to actually
make sure that we solve it
faster than we otherwise would.
And at the end of the day, it
all comes down to these things.
The first thing is,
ultimately it all costs money.
10 years ago, 15 years
ago, when I started out,
I had three problems to solve.
I need a plan for
how to solve aging,
and that's what I've
been telling you today.
I needed people.
I needed the
world's best experts
in the various
scientific areas to be
enthusiastic about
working on this.
And that, I have demonstrated.
We already have now, very much.
But, at the end of
the day, these people
are still, by and large,
sitting on their hands,
waiting for the resources
to actually get on with it.
Because we only have perhaps
one tenth of the budget
that we would need to be
able to fund everything
that really needs to be funded.
And that is absolutely the
number one problem right now.
Obviously, I'd like
you to learn more.
I've only had an hour.
That's not nearly enough time
to do justice to all that we do.
Anyone who wants to get involved
in terms of actually learning
more about it through our
educational initiative,
please go and have a look
at that at the website,
at sens.org.
But ultimately, it's
all about advocacy.
Hands up.
Anyone here who
doesn't know anyone
who's richer than you are?
All right.
So it's all about changing
people's minds, right?
It's all about changing
people's minds.
The more people we
have on-side, who
understand about the
importance of this mission,
the faster it's going to happen.
And I spent a lot of
my time getting people
to understand how
important this is.
If the people that I were
able to bring on-side,
were to go out and bring
other people on-side,
and so on and so
forth, we would solve
this problem a
great deal faster.
I wrote this book
several years ago.
It's very comprehensive.
I call it semi-technical.
What that basically
means is you don't
have to be a trained
biologist to understand it,
but you probably won't be
reading it in one sitting.
It's quite dense.
It doesn't cut any corners
at all on the science.
And it was written
several years ago.
But it's still
fairly up to date.
That is not because
there has been
inadequate progress
in the meantime.
The progress has been wonderful.
But what it is is
because the progress
has been pretty much the type
of progress that we predicted
would happen.
In other words, this is, again,
another piece of evidence
that the SENS paradigm is
standing the test of time.
So that's all very heartening.
I think I should
also mention this.
Incidentally, if any of you
are going be in California
a few weeks from now--
but I guess you probably
have friends who are-- and
anyone that you might want
to recommend to come
to our conference,
I would very much
encourage you to do that.
This conference is happening
just-- maybe 10 miles south
of the Googleplex,
August 21st to 23rd.
And, of course,
it will cover all
of the science of
what we're doing,
of rejuvenation biotechnology.
But also we'll have
extensive participation
from industry, from
regulatory people,
from policymakers, and so on.
So it's going to be
quite a gathering.
And, of course, lots of
laypeople there as well.
And I very much encourage
you to encourage other people
to do that.
I'll stop there.
And I think there's probably
a bit of time for questions.
Thank you very much.
[APPLAUSE]
AUDIENCE: Hi.
So in the field
of cancer, we see
that there are some cancers
that have been very-- well, have
been tackled extremely
well in the last 100 years,
others that become
very resistant and very
difficult to deal with.
Do you see the same things
likely to happen when we tackle
aging more generally, in
that some diseases will be
eradicated quickly and
others will take a much
longer time to get rid
of, and a long tail.
AUBREY DE GREY: Yeah.
That's a really great question.
So first of all, let me give
you my take on where cancer sits
within the whole universe
of problems of aging.
My view is that concept
is by far the hardest
aspect of aging to fix.
It's the one that has natural
selection on its side.
And that makes it--
any cancer that's
big enough to be
clinically relevant has
a trillion different individual
engines of genetic creativity
in it.
It's really a
tough nut to crack.
Now a lot of people, because
of largely the kind of evidence
that you described,
they don't like
to think of cancer as a
single disease anymore.
They like to think of
it as family of diseases
that we just happen to give
some collective name to.
But the fact is that's
not really fair.
Because there are some things
that cancers have in common.
And in particular,
there's one thing
that absolutely all cancers
have in common, namely
the fact that they need
to figure out a way
to grow the ends of
their chromosomes.
Chromosomes get shorter
when a cell divides
and there needs to be a
way to compensate for that.
There's only two ways that
cancers ever use to do that.
And we're well on
our way to being
able to stop that
from happening.
So that's essentially the way
that we're going about it.
In general when you talk
about the relative degree
of difficulty of coping
with aspects of aging,
I think you're right.
There are definitely things
that are harder than others.
And actually, the last
part of the reason-- well,
in fact, most of the reason why
SENS Research Foundation was
set up, was precisely to
mitigate that problem.
To ensure that we work
on the hottest things
and that they don't
get left behind
and we just fix the easy things
and end up where we were.
AUDIENCE: Thank you.
AUDIENCE: If you had
like a crystal ball,
how long do you think it will
take until you've got something
that you say actually we'll
be able to live for 100 years?
AUBREY DE GREY: Yeah.
You ask that question
in exactly the way
that an engineer should ask it.
In other words, I haven't
the slightest fucking clue
because it's a long way away.
But, of course, you
want an estimate.
And actually you're quite
right to ask the question.
Because a lot of gerontologists
would just refuse to answer.
They would say it's
irresponsible to get people's
hopes up, or
something like that.
And I say, on the contrary,
it's irresponsible
not to give an estimate because
however bad my estimate is
going to be, yours is going
to be even worse, right?
And therefore, I'm got to give
as good an estimate as I can.
So my estimate is this.
I think we have at
least 50/50 chance
of getting the technologies
that I described today
working reasonably well within
the next 20 to 25 years.
AUDIENCE: Yes.
AUBREY DE GREY: Right.
And the technologies that
I describe today I think
will probably give about
30 additional years
of healthy life.
And, of course, they
will give those years
to people who are already in
middle age or older, 60, 70,
or even maybe 80, at the time
that the therapies arrive.
So that means most
people in this room
have a relatively good
chance of benefiting.
Two caveats.
The first caveat,
everything I just said
is only going to be true if
research in the next five
or 10 years goes a lot faster
than it's currently going.
The funding limitation
that exists at the moment,
I estimate is
slowing things down
by roughly a factor of three.
In other words, over the past
10 years, the amount of progress
we've made towards getting
proof of concept of these things
in the lab and so on, has
probably only advanced
by about three years
relative to where
it could have gone if only
science had been limiting.
The second caveat is
the probabilities.
So I can tell you
the 50-50 estimates.
But I want to tell you right
now the variance is high.
I think there's at
least a 10% chance
that we won't get
there for 100 years.
But who cares?
A 50% chance is perfectly
enough to be worth fighting for.
AUDIENCE: Yeah.
Thank you.
AUDIENCE: Thank you very much
for this very interesting talk.
AUBREY DE GREY: Thank you.
AUDIENCE: Actually
about a year ago,
we set up this company called
Calico, the California Life
Company.
And we set it to up
work independently.
And I was just
wondering, first of all,
how do you view
this development?
And secondly, if you
already had the chance
to work with them so far?
AUBREY DE GREY: Yeah.
Actually, I was very
surprised that no one
at the talk I gave at
lunchtime asked about Calico.
But, yes, Calico
was, as you say,
set up my Larry and
Sergey about a year ago.
Well, my view of
that development
was expressed in
"Time" magazine, which
was where the thing
was announced.
"Time" got me to write the
reaction piece, so to speak.
And I was pretty effusive.
I was overjoyed.
And I am still am.
I think there is a very
respectable chance that they
will make a really big
difference, but only a chance.
It just remains to be seen.
They are taking their
own really good time
to decide exactly
where they're going
to be prioritizing
their efforts.
And in a way,
that's a good thing.
The worst thing
that could possibly
would have been a repeat of
what happened 15 years ago when
another very wealthy
individual, Larry Ellison,
decides to do essentially
the same thing,
albeit in a foundation,
rather than a company.
He basically went out
and promptly hired
a veteran gerontologist
from the NIA.
And the result was
completely predictable.
15 years and $400 million
later, absolutely nothing
had been done that wouldn't
have been done anyway.
And he's given up now.
So Calico is potentially
a really good thing.
They've got people at the
top who are, by and large,
not trained gerontologists.
And therefore, they know
what they don't know.
They're making
their own decisions.
They're not talking to us nearly
as much as we'd like them to
and as we think they should be.
But that may change.
So I'm hopeful.
AUDIENCE: Thank you.
AUDIENCE: Hey, Aubrey.
If, as you describe,
this might become
one of the biggest
industries ever--
AUBREY DE GREY:
The very biggest.
AUDIENCE: And if,
as you describe,
you've done a great job
of convincing people
that it is worthwhile
fighting for it, what
are, in your opinion, the three
main obstacles to actually get
the necessary
funding going, which
seems to be one of the
biggest problems on the way?
AUBREY DE GREY: Yeah.
I will actually just stick
with one main obstacle, which
is something that
I historically used
to call the pro-aging trance.
But my marketing people tell
me that that's too derogatory.
So I'm not allowed
to say that anymore.
Essentially it's fear.
It's a combination
of two types of fear.
Number one, fear of the
unknown, recognition
that a post-aging world would
be very, very, very, very
different.
And therefore, maybe we ought
to stick to what we know.
Kind of essentially
the same as what
happened to resistance to
the Industrial Revolution.
And secondly, fear of
getting their hopes up.
People just are not willing
to reengage this battle.
People, in general, have
made the peace with aging.
They have accepted defeat.
And when you've accepted defeat,
the last thing you want to do
is go through all
that stress again.
So that's basically
what it's all about.
People who are otherwise
perfectly well educated
and perfectly rational in
absolutely every other walk
of life, will say
things and think things
that they would be embarrassed
to say to a small child
to shut them up, when it comes
to this particular topic.
And, of course, the
problem is that I
don't get to talk to everybody.
Time and time again, I will
be in the company of people
who are not only get
it, but say they get it.
And they will tell other
people that they get it
and that things are good.
But do they actually run
me a check, not as such.
Why do they not
write me a check,
probably because their
wife doesn't want them to.
AUDIENCE: Hi.
The cost of gene sequencing
has decreased kind of massively
over the last 10 years.
And I've seen various
depictions of people
saying that in five
years' time, we'll
all be getting our gene
sequenced for the cost of $10,
or whatever.
Do you think it's a
high chance that we
might find genetic causes
for all these problems,
like Alzheimer's,
before we find solutions
that involve damage limitation?
AUBREY DE GREY: Yeah.
Great question.
So I'm going to answer it in
a slightly complicated way
with two definitions
of the word "solution."
There will be the
possibility of identifying
genetic factors that are
responsible for the age
of onset of certain
age-related conditions,
whether it be Alzheimer's
or anything else.
And then also the possibility
of genetic conditions
that are simply responsible
for it in a binary way,
for it happening
or not happening.
So what I can tell you
is that it's very likely
that we will find the former.
Albeit, it's not nearly
as easy as people
were thinking
maybe 20 years ago,
when [INAUDIBLE] was discovered.
And it looks like
it will involve
a lot of different
genes combining
in different people, each
individual one of which
only makes a small contribution.
However, we can say
definitively at this point
that the answer to the
latter question is no.
That the aspects of
metabolism that ultimately
drive the accumulation of
these various types of damage.
And therefore the eventual
arrival of these pathologies,
are non-negotiable.
Now, the number one
worse thing that we have,
that drives all these
things, is breathing.
Breathing is really bad for you.
But there's not a lot of
choice that we have about it.
AUDIENCE: Thanks.
AUDIENCE: Hi.
You talked a lot
about sort of funding
and where you get
it from and also
bringing in the
private market narrows
the diversity of the research.
So at what stage do you
go to the private markets
and the venture capitalists?
AUBREY DE GREY: Yeah,
a great question.
I'm not really sure about
narrowing of diversity.
I mean in a sense the
continued existence
of nonprofit participation
in all of this
is a good protection
against that.
So individual
components of the range
of things that need
to be done might
go into the private sector,
without necessarily restricting
the ability of other components
to continue being developed
in the philanthropic
sector, so to speak.
That's kind of how it going.
I think we may be done.
More?
AUDIENCE: Hi.
This may not be of
interest to you at all.
But sticking you with your
car analogy, if you take a car
and you drive it
on a smooth road,
and you keep it away from Sun,
and you put in the right stuff
that it needs in the engine
and what's in everything,
it probably accumulates
less damage.
If we look at that
for a human being,
in the meantime, before your
research is going to save us
all, what can we be
doing to damage limit?
AUBREY DE GREY: That's an
absolutely excellent question
and an absolutely excellent
way of expressing the question.
Because you're absolutely
right, in the case
of simple man-made machines like
cars, lifestyle matters a lot.
You can drive a car carefully
and well and it will last a lot
longer-- quite a lot
longer than if you don't.
The unfortunate fact
is that it's not
quite like that
for the human body.
When I mentioned a
moment ago that breathing
is really bad for
you, breathing and
the other non-negotiable
aspects of being alive,
like eating-- eating anything,
not just eating badly--
are the overwhelming
majority of the drivers
of the accumulation of damage.
Of course, there are things that
you can do that are obviously
bad for you, like smoking or
getting seriously overweight,
but nothing you mother
didn't tell you.
If you're basically
averaging healthy,
then the amount of
additional postponement
of age-related ill
health that you
can achieve by any kind
of lifestyle, or diet,
or exercise modifications,
or whatever,
is, as far as we can
tell, really tiny.
And therefore,
there's only one way
out of this, which is to hasten
the development of therapies
that we don't yet have.
In other words, give me
large amounts of money.
[LAUGHTER]
Thanks very much everybody.
[APPLAUSE]
