Kind: captions
Language: en
you are living in the most disruptive
time in human history given the advances
in Ai and biotechnology you might have
to contend with the possibility of human
immortality it's certainly not a
guarantee but advances in health span
anti-aging and cellular biology make it
one of the most important conversations
of Our Time Investments and decisions
made now will reverberate for
generations to come here to talk about
the State of Affairs is Dr Bill
Green you as an investor have a very
difficult job and as an investor you
have to bet against the consensus and be
right so what I want to know is what is
it that you really believe in in your
specialty of Biotech that you're willing
to bet big on
fundamentally we're here to invest in
people and companies and ideas that are
going to lead to real breakthrough
Therapeutics that can treat delay and
even prevent diseases of Aging more
broadly in biotech we're here to create
the next generation of therapies that
are safer more effective and more
tailored to the actual problem that
individuals have as opposed to really
broad
populations and that's exciting how far
are we going to be able to push it so if
we can slow down aging I'm sure we can
both agree on that the question becomes
can we stop aging can we reverse it the
short answer is absolutely we know we
can in
worms sometimes in
mice can we do it in humans at the level
of our cells yes can we do at the level
of our whole
body maybe the question is do we want to
what we really want to do is live our
lives in health with vitality and not
spend increased ing portions of Our
Lives debilitated by chronic disease
that's what most people really think
about they don't they don't necessarily
want to live forever but they definitely
want to live healthy I do most of us do
and that absolutely has a has a role to
play with the biology of Aging with
slowing down the processes by which
aging if you will goes wrong I'll be
very eager to have the debate about
whether we should want to or actually
live forever but first I want to know so
given that you're looking at this
there's a real shot that we're going to
be able to uh we know we can reverse it
in a Cell but there's a shot that we
might be able to as we get more
breakthroughs do that at the level of
the whole body what is the BET as you
look at this as an investor there's
going to be a few things on the table
that you think okay it's maybe one of
these and I'll make this number up but
maybe one of these five things what what
is that small handful of things that you
think have a real shot to be a
blockbuster some of what uh really leads
to chronic disease and degenerative
disease is fibrosis it literally instead
of being pliable and and resilient our
tissues can get fibrotic and and and
connective tissue builds up and and
actually
not only reduces the ability to move but
actually reduces the function so think
about your heart which has to beat every
second uh if it if it becomes fibros it
can't expand it can't relax it can't
beat strongly and that that's one of the
causes of heart failure if we could
actually re and we've thought that that
fibrotic process is a one-way Street
once it starts you maybe can slow it
down but you could never stop it or
reverse it
if we could reverse fibrosis we could
unlock a lot of resilience in our organs
and tissues and that could actually
reverse some of the diseases of Aging is
there anything that we see in the
research that that's promising like is
somebody actually working on this lots
of companies are working on it and uh
even more
encouragingly uh researchers from a
variety of biology perspectives are
really looking at the connection between
chronic inflammation and and how that
leads to fibrosis and looking at that
edge of how does it become how does it
cross that line from I'm inflamed to I'm
actually building up unhealthy
connective tissue and and being and
becoming restrictive uh so there's lots
of research going on there there's lots
of scientists working on it I can't say
today who's going to find the exact
right thing but I'm highly confident
that given the thoughtful thoughtfulness
and investment in research that we will
have several ideas to try out as
Therapeutics and one of them may well
work how do you evaluate a company so
for people listening that don't know a
lot about biotech investing uh it's had
a brutal bare Market the last couple
years some people think that maybe we're
beginning to thought out again going
back to the idea you have to be able to
bet against the consensus and be right
how do you look into this are you
evaluating the entrepreneurs are you
evaluating the science how do you
develop confidence when the world thinks
you're
crazy you have to be a little crazy to
invest in biotechnology because there's
so many ways that things can go wrong
and at its heart while we study the
science we utilize the science we
exploit the science we don't know all
the science so by doing clinical trials
by developing a drug it turns out we
discover for more science unfortunately
sometimes that means the answer is no
so at its heart we invest in people it's
people that make this work it's people
that that figure out the science it's
people that use what they're learning
along the way to go back and question
their assumptions and refocus to find
the right path if they find they're on
the wrong path that's a hard that's a
hard skill it's a rare quality and
that's what we look to invest if we find
those people and help those people
create companies there's a definitely
higher chance of success what do you
think about somebody like Elon Musk so I
don't know how much you know about my
background but I started out as an
entrepreneur uh had to learn business
and when I look at Elon I see somebody
that is a once in a generation maybe
even less than that mind in terms of his
ability to actually get something across
the finish line and I am a gast Bill a
gast at the number of people that look
at him and see um a loose cannon
somebody that can't be trusted uh people
throw Shad at him as an entrepreneur you
didn't found this out or the other uh if
I'm running my human evaluation
algorithm on him I come back it's just
all green lights even though for sure
he's going to get things wrong there's
no doubt about that uh but he from just
a track record perspective and ability
to process d data quickly um he falls
into a very elite category but even he
despite the number of billion dooll
companies that he has been a meaningful
contributor to uh there are still people
that discount him so what does your
algorithm look like as you evaluate an
entrepreneur and use him as an example
so I can understand how you think
through
this with the caveat that I don't know
Alon musk personally
uh I'm inclined to agree with you that
he almost he must have a a once- in a
generation mind and uh is incredibly
smart incredibly driven and clearly is
able to to organize people drive people
and get things done there's no question
those traits are necessary in any
entrepreneurial activity and absolutely
necessary in biotech
too in
addition what's a little different about
biology and biotech compared to broadly
speaking Tech is often in
Tech we know the science we know the
physics the question is can the
engineering work can we actually make
something that will do the thing that we
want to do in biotech we don't have
perfect knowledge we actually don't know
at the end of the day whether if we get
all the science right get the
engineering right get the clinical
trials right if it will actually work
until we do the experiment in people and
that is a that's a that introduces a
couple things that are different one
there's a tolerance for for risk that
and embracing of of that kind of risk
that you just have to take and we have
to be data driven we have to actually
accept the fact that sometimes we learn
that biology is going in a different
direction than we thought and that's a
little different in
we can't just force that we can't force
or cajo that to be different the other
thing that's that's a little different
sometimes is when we're talking about
making Pharmaceuticals and making
biotech drugs we are talking about
people we do have to be really
thoughtful about how we design clinical
trials who we put in clinical trials and
that's that's just another dimension
Beyond pure entrepreneurship that we
have to take into account so uh all the
entrepreneurial and uh Brilliance lights
flash green for me totally agree with
you in a biotech setting you have to
have all that and then also the ability
to learn from the science um except that
you might have to really retrench and
refocus and go in a different direction
and uh really pay attention to how we're
going to protect people as we as we do
those clinical trials I think that to me
is exactly so what I hear you describing
as basically first principles thinking
you have to go in look at the data you
have to make sure that you're
understanding what's really happening
you have to be willing to adjust to that
that to me in a nutshell is what makes
Elon so fascinating is he thinks from
first principles so when I talk to
budding entrepreneurs about you know how
are you going to be successful it's what
I call the physics of progress the
reason I call it the physics of progress
is it it I really believe that it is
foundational uh I'll I'll lay it out but
I don't think there's anything beneath
this and for people that haven't heard
of first principles thinking it's
getting Beyond analogy you're getting to
the actual root physics of the situation
so progress to me happens in the
following way um you're going to come up
with a guess as to how to overcome an
obstacle to reach your goal so uh you
need to know what your goal is you need
to know what's currently stopping you
like why will you not just automatically
get to your goal entropy is one easy way
to think about it the world's just
working against you in a thousand
different ways whether it's biology and
it's incredibly complicated whether it's
humans in a biotech uh setting where
they're just not being compliant um
other companies that are trying to scoop
you and move faster whatever it is
there's just going to be a lot of things
working against you so you have to
identify I know where I want to go I
know what's standing between me and
getting there and I'm going to come up
with my best guest on how to overcome
that you're going to need to come up
with uh a point of data that you're
going to use to determine whether you
actually move towards your goal or or
not and then you're going to run a test
and you're going to try that thing that
you came up with and it's probably not
going to work as well as you wanted to
but you're going to learn in that
failure and then you're going to start
over and you're going to be a little bit
more informed you're going to come up
with a little bit better hypothesis
maybe a slightly different metric by
which to judge it you're going to run
that experiment it's going to fail again
and you're just going to exist in that
Loop the reason that Elon seems utterly
fascinating to me and for people that
don't know uh he has a company called
neurolink and they are trying to do
effectively computer brain interfaces so
he is somebody that's very much in the
biotech space as well as many other
spaces um and when you hear him talk
that's his process he wouldn't call it
the physics of progress obviously but
you're just you're trying something
you're iterating you're learning you're
getting your ego out of the way um in
order to build upon that
so if we agree that that is the only
path forward and if you see another path
now is the time to tell me uh but if we
can agree that that's the only path
forward how do you figure out if the
person you're sitting across from is
actually going to be able to do
that great question
and boy I wish I had an algorithm that I
could write on a 3x5 card so I could
interview potential CEOs and say ah got
it ABC uh it's it's it's hard um and
it's hard in part because no one goes to
school to study how to have those
qualities that ability to be data driven
that ability to wash rinse repeat and
and get it a little bit better and a
little bit better and have the
fortitude uh to to be able to do it and
to
communicate effectively with
stakeholders why we're doing it this way
and why we took that step and why we're
taking the next step uh I it's it's hard
and I think it's a relatively rare
skill the the algorithm that I use
personally is asking people about what
adversity they've faced in their lives
and professional sometimes personal but
certainly professionalized how they
worked around it uh what what they did
in the face of
failure uh success what's the right
answer to that question
there's more than one right answer
absolutely
um the right answer that I really like
is it hurt I was
sad I had to take couple days and really
think about why am I doing this but then
I then I thought about it and I thought
there's another path forward what I have
to do is this what we have to do as a
team is that whatever it is and then we
went and did it and and it was hard but
we got
somewhere that's an answer I love to
hear now there is a very hard reality to
be faced in entrepreneurship and in fact
let me set the stage for people so
according to your own website and I've
heard you answer this question before so
I know what you're going to say but
according to your own website you guys
have up to a billion dollars a year to
invest um with the goal of making Health
span available to everybody that gets
complicated and I'm sure we'll talk more
about later but the reason I bring that
up now is you have a lot of money and by
biotech standards you guys are arguably
the biggest player in the space and as
the chief investment officer you're the
one that's going to have to make a call
on a lot of people uh and with no sort
of easy answer you have to accept that
even if the person gives that answer
there is just a sense of raw intellect
and I have interviewed to hire I've
interviewed over 1500 people which
doesn't sound like a lot unless you're
an entrepreneur and you know just how
many hours that is um and what I've
learned is that hiring borders on
Impossible and that the situation is so
artificial that the only way for me to
know if somebody's going to be good is
to actually work with them for a while
so we ended up building in a 90day
probationary period my default answer is
no I know what metric tricks you're
going to need to hit for me to be
comfortable moving outside of the 90-day
window but I really need to see are you
smart and I'm looking for people that
are really smart and if you know my
personal philosophy that makes me deeply
uncomfortable that that's a thing but
that's a real thing um I'm also looking
at not just resilience which is what you
described I'm looking for raw
unadulterated Obsession I'm looking for
somebody that borders on mentally ill
that they they are so all in that
nothing is going to stop
them I'm going to guess given your
experience you know those things to be
true so my question becomes how when
you're not hiring somebody how do you
get to know them well enough to know if
they're just giving you lip service in
the meeting or if they really have what
it takes to um plow through what could
be 10 years of sort of blind faith that
you see something other people don't and
that they'll overcome the nigh
insurmountable obstacles that are
inevitably going to come their way yeah
important topic uh important topic in in
anyone's work life uh and absolutely in
ours uh I'm going answer that in just a
question in just a moment couple things
about what we're doing at Evolution from
an investment standpoint that I think
can be helpful uh one of the challenges
in biotech is as you
mentioned experiment fail iterate
experiment fail iterate move ever closer
uh with each cycle to the ultimate goal
is absolutely important in biotechnology
when each of those experiments or each
of those efforts is uh a clinical trial
it's expensive and uh one of the biggest
challenges possibly the biggest
challenge in biotech
is even if you're on the right path
getting more Capital to to do the
experiment enough times to get you there
is really hard investors are fickle uh
even Venture capitalists are a little
bit fickle they're they have to be they
need most your average Venture Capital
firm has to obviously make money it
needs to make money in a certain time
period it's more patient than
highfrequency trading but it's not
infinitely patient Capital so one of the
things that we bring as impact investors
into the space is the ability to support
companies and entrepreneurs through more
Cycles uh to to hopefully give them the
chance to succeed where other sources of
capital might not initially give it to
them so that's a that's a real
intentional piece of why we have an
investment function and uh why we're
we're supporting it with with to the
extent that we are because we think this
this space new space difficult biology
new bi biology needs companies need the
ability to to iterate more than once and
to get more than one shot at success if
they have the right people in the right
science and so we're here to support
them for a longer period of time if that
makes
sense
uh to to answer your question about how
do you get to know leadership teams uh
and development teams of Biotech
companies to to both assess whether they
have the the raw Obsession and the
resilience to get there and to help them
to build more of that into what they do
uh it takes time um one of the things
that's challenging that's been many
things have been challenging about covid
but being on boards in during covid uh
is only superficially convenient because
you do board meetings over Zoom but uh
there's a real piece that you miss by
going and being with your leader
leadership team in person spending time
with them having dinner and lunch with
them standing around having coffee and
actually talking about what they did
over the weekend what's happening at
home how they're integrating their work
life uh both professionally and
personally those
three-dimensional ways of of
understanding people are what give you
the opportunity to catch them doing
something right which reinforces all the
things we want to reinforce and
entrepreneurs and help them course
correct if you can see something that
that they can be coached
on do you know who John Wooden is the
coach yes yeah okay so John Wooden
famous college basketball coach um I
don't think this is an apocryphal story
but even if it is it's very interesting
he said he used to spill water behind a
star player and then see how they would
respond he would have like the um tow
boy spill water and he would see how
people would respond to them and if they
were kind and courteous then he was like
okay cool I know this player has
character and if they were um a jerk and
mean-spirited then he was like no matter
how good of a player I can't have
somebody that brings that attitude um is
there a similar spirit in entrepreneurs
that you look to to see um that they
have the it Factor that's going to help
them be successful
100% this is uh thank you for asking
that question I didn't know that story
about John Wooden but I love it
uh I don't provoke CEOs and and biotech
Executives by uh doing something
annoying and seeing how they'll respond
uh although it's not a bad idea I um
absolutely look for the no job is too
small attitude I love leaders who come
from a service
mindset uh if I see a
CEO making coffee for people
people putting new paper towels on the
paper towel roll staying late to uh
being the last guy out of the office not
because he's driven I mean yes he's he
or she is driven but also because
they're cleaning up from from the day I
love that uh I absolutely love the no
job is too small uh attitude and I think
that leaders who come from that place
Empower their people to think no job is
too big for them if there are a um few
buckets in front of us of what you think
is is actually going to push healthspan
forward what do you have the most
conviction
in I think there's almost no question
that addressing chronic inflammation as
a root cause of chronic disease uh will
yield some really inter in and hopefully
uh breakthrough
therapies uh I also have a real belief
that next
Generation uh next there's some Next
Generation technologies that are going
to really have potentially have an
impact here and by that I mean the kinds
of technologies that can yield more than
one kind of therapeutic so getting away
from one disease or one approach to
disease we've seen that Gene editing is
really exciting there's been a lot of
investment first therapeutic has gotten
approved in gene editing that's good but
that of course that's pretty permanent
that changes your genetic
makeup uh We've also seen in in the
longevity and health span World a lot of
interest in cellular reprogramming
actually going and taking cells and
moving them back to a more youthful
State really exciting but also sort of a
blunt instrument uh you're changing the
whole cell which could have um all sorts
of effects good and maybe less good I'm
really excited about what's the next set
of advances in manipulating the genes
and the cells that will take all the
best things from those
and and be really applicable to the long
term for broad populations we talk about
the epig genome a lot in aging so the
genome is your DNA it's the blueprint of
of how you're built and what you do the
epigenome is how those genes are
expressed and there's Dynamic control
over your life about gene expression
goes up gene expression goes down and
there's lots of paths that the body uses
to manipul to change that and those
controls over not are you driving a car
and is it a car or a submarine but how
how fast is the car going is your foot
on the gas is your foot on the brake
those those kinds of processes are
really important for aging and if we
could
control the epig genome if we could edit
the epig genome the way we can edit the
genome we might have a more Dynamic way
to change the the expression of cells
and to therefore maybe temporarily move
them to a more youthful state or only
move part of the cell to a more youthful
State and that potentially could have
wide ranging impact over time this is
not an overnight thing but over time
that sort of approach could be really
important for chronic diseases so I'm
really excited about people doing
fundamental Research into how we can
manipulate cells to get them to do the
right thing in a more Dynamic way okay
this is really interesting um there was
a recent study that came out of Harvard
that took mice and
uh I think genetic or bred them to have
a predisposition to breaking in the DNA
because the fundamental question was uh
is this a DNA mutation problem where hey
you get an x-ray you fly you're exposed
to all these things that are damaging
your DNA and aging is basically the
accumulation of these mutations where
we're just putting the DNA back together
in the wrong way or is it something to
do with the epig genome where the as
this starts to get complicated but but
the way that you're marking the DNA for
what genes to express is called
methylation so your genes are tightly
bound up and you basically loosen parts
of it to say I'm a skin cell I'm a heart
cell I'm an eye cell whatever
differentiation uh the theory went that
it's either all of these gene mutations
in the DNA that are causing the problem
or it's the way that they are getting
marked uh so that they're basically
dedifferentiating so now instead of
being clearly an ey cell and the wrong
part of it has become loose and is
expressing itself and uh this very
clever experiment showed that even these
mice that their DNA is constantly
breaking and needing to be repaired at
the end when you looked at their DNA it
was the same it wasn't accumulating a
bunch of mutations instead what was
happening is that we were getting
dedifferentiation the methylation the
the bookmarking to use a very layman's
term that you may hate uh is the
and so um that to me makes a lot of
sense that you're really excited about
this but what I want to know is okay one
do you think that would you be willing
to make the declarative statement that
the epig genome errors in the epig
genome is
aging
ah
absolutely the only caveat I'd say is
that's not the only process process of
Aging it's not the only different
different um definition of Aging but it
I believe it is a definition of Aging it
is one of the processes that is aging
and when expression through the
epigenome when control of the epigenome
goes wrong that is absolutely I believe
one of the ways that aging goes wrong
and we get disease so it's one of the
pathways that's really important okay so
what are let's go through the Hallmarks
of Aging I've heard you talk about
something I have not heard other people
talk about which is emerging Hallmarks
of Aging so I'm going to guess it goes
something like this there are the things
that we know and have already named and
you're going to tell us what those are
known as the Hallmarks of Aging wrinkly
skin being the one that everybody can
see much to my dismay uh and then you've
got things that we're just now
discovering is what I'm guessing you're
going to call the emerging Hallmarks and
then I would love to one lay those out
and then uh the last part of this is
understanding which of those do you
inker controlled by the epig genome and
then since you're not willing to say
that that is the sum total of Aging what
sits outside of
that well this is a great conversation
and there might be a job for you at
evolution in our science department
actually helping create that future we
think about these things
so the term Hallmarks of
Aging refers to a set of ways if you
will that the cell can go bad over time
uh in response to all the slings and
arrows and insults that cells are
subject to as as we live our lives um
things can start going wrong DNA can
break of course uh when DNA breaks
accumulate uh enough and don't get
repaired enough in my mind that sends
you down the path of
cancer uh when theep genome breaks that
sends you down the the path potentially
of cancer but but certainly of these
chronic diseases and aging but there are
other ways that uh that cells can can go
bad if you will uh they
can lose their ability
to fold proteins correctly to actually
create the architecture that they need
to create and like any other structure
if if you don't if you don't put the
pieces of wood together you don't get a
house you get something crazier uh so
misfolded proteins is is a is a real
Hallmark of how cells can go wrong and
that can lead to aging the ability to to
clean house if you
will so over time uh proteins get
misfolded and some things get created
that that don't work out or they just
break and the cell has to renew itself
and actually clean house and clean up
messes and and do constant upkeep like
we have to do on our houses um the
ability of cells to do that is is
critical and if they lose the ability
which we give fancy terms to like
autophagy which is literally eating the
cell eats the misfolded proteins if we
lose that ability that's another way
that we lose the ability to renew and be
youthful uh yet another is energy cells
need energy uh the battery if you will
cells are these uh organel called
mitochondria and if the mitoch the
mitochondria do a lot more than just be
batteries but think of them as a battery
in your cell that provides
energy if the battery runs down can't be
recharged anymore you need new batteries
but we're not great at making new
mitochondria that that are youthful we
can make new mitochondria that don't
work as well as they used to so uh
mitochondrial biology is another
Hallmark of Aging so these are examples
of ways the if I if you will the
original Hallmarks of Aging were how do
cell
processes go wrong and how does that
lead to aging on the emerging side first
of all science marches on we're learning
more and
and uh always and some Hallmarks of
Aging may be less Hallmark maybe they're
more consequence than cause and one
example that's been potentially
controversial in the in the Aging
biology world is tiir we've heard a lot
about tiir shortening so is teir
shortening a cause of disease or is it a
marker that bad things have happened
don't know uh but to the extend the
latter then maybe teir shortening isn't
as much a Hallmark of Aging as some of
the other things that are more
fundamental uh but thing but new science
will bring new processes in we'll learn
more about how cells work and there's a
constant process on the uh academic
science and thought leader side on what
what are some of these other things
we're seeing cells do and could they be
Hallmarks of Aging the other way that I
like to think of Hallmarks of Aging
though is to get out of it's It's about
cells but it's not all about cells aging
is as you said is sure people should
care about their cells I guess but it's
pretty hard to tell people you should
think about your cells you can
definitely tell people you don't want
wrinkly skin right do this but if you
say you don't want to lose your
autophagy so do this that's a harder
cell
um but aging is is so much more than
cells what about intrinsic capacity what
about Vitality which let's make that
more biologic muscle strength the
ability of your muscles to recover after
exercise and self-renew and be strong
what about your senses uh what about
cognition broadly and biologically it's
not just about neurodegenerative disease
are there ways in which we could look at
the
biology of the Aging brain and and ask
can we enhance cognition biologically
and uh
to embrace if you will those as
Hallmarks of Aging to
worthy of the same scientific treatment
worthy of the same focus and worthy of
of Therapeutics development when you're
looking at the complexity of all of this
stuff how do you think we're going to be
able to begin weeding through this stuff
uh for me AI feels like the closest
thing that we have to a magic cure so if
any sufficiently advanced technology is
indistinguishable from Magic I would say
that we're we're getting pretty close to
that and we're filming this not long
after the um the firing of Sam Alman and
the near immediate rehiring of Sam Alman
and there is a lot who's the CEO of open
AI um and there is a lot of debate about
whether um their new thing I think
called
qar uh is Agi and that that spooked
everybody and that's why they fired him
and this is really a battle around
safety um but what what do you think
about about that how much of a
difference do you think AI is going to
make how much does that fall into your
investment thesis um and and you know as
as all the things you just laid out are
incredibly complicated and it feels like
we're sort of at base camp of Mount
Everest and we have a long way to go um
does AI feel to you like the elevator to
the top of Mount Everest that it feels
to me for me AI is a
tool it's a great tool potentially used
well like any tool
uh
harnessed and exploited and and adapted
I think
AI is already an important tool in in
drug Discovery uh and can be even more
important to to your
point it's possible for for folks like
me to make things sound real complicated
but at the end of the day the way we
make progress is by breaking things down
into doable tasks take that Hill take
the next Hill take the next Hill
uh we don't I don't stay up at night
thinking this is hopelessly complicated
I'm I'm drowning rather it's how can we
address this question to answer that
question to make that thing work so that
becomes then uh a set of addressable
problems a set of addressable puzzles
and AI is a remarkable tool for reducing
complexity it's one of its best things
one of its best most validated uses and
to reduce complexity in what's the
Hallmark of aging and what's the
connection between autophagy and wrinkly
skin that's where AI is having a role
today in in our world and will have a
really big role Tomorrow there's no
question so is it the uh is it the
elevator to uh to from the base camp to
the summit I'd say uh it's the fixed
ropes you get to the next level and
instead of being presented with oh boy
it's windy it's really steep uh I'm
afraid I'm going to fall off the
mountain oh there's a rope I can grab
onto that and pull myself up and guide
myself along now I'm feeling more
surefooted I like that that's a a good
analogy so um let's talk about those
questions that we have to ask and answer
in order to get where we want to go um
do you have a sense of what they
specifically are the goal is to make it
linear so you're you're suggesting
perhaps that there's a linear process we
figure out the biology that translates
into mice that translates into people uh
and that translates into drugs which
translates into prevention um the goal
is to make it as linear as possible but
what are the specific linear steps
so
uh looking at the early side we really
need to understand as much cell biology
as we
can answer the questions about how these
Hallmarks of Aging work together how
they interact uh how one leads to
another and
importantly can we not just
ask if we stop this bad process will
celles get better because we know the
answer is yes
but rather to ask if we
intervene late there's already some
damage because how do we know we know
that uh we know that we're getting a
disease when there's either a sign or a
symptom so can we use that biology in
whichever Hallmark of Aging one wants to
talk about or whichever biologic process
mitochondria fibrosis whatever it is
that you want to do can we can we find
ways to start when the damage has not
become permanent but already started and
move things backward so that's a
that that opens up a whole set of of
inquiry at the at the early science
level professors in Labs uh uh
entrepreneurs in Labs asking fundamental
basic questions about how cells work uh
that doesn't look like a drug yet um and
there's a lot of work happening in that
area and we need to have more of that we
at Evolution are funding new and
emerging scientists to ask questions
that we don't even know how to ask
yet but um we want to know if we can
intervene if we can if we
can if we can make mitochondria work
better if we can uh restart autophagy if
we can restart the process of of
refolding unfolding and refolding
misfolded proteins so there's some very
specific sets of basic questions that
that uh uh scientists and Labs need to
answer then really
important uh are the questions about
translation we can't go we never could
go and we never will go from even with
AI even with the best AI from uh we
predict this chemistry will do this in a
cell let's put that in 5,000 people and
see what happens oh there's there's some
stuff we got to do in the middle uh we
certainly have to do our best to predict
whether it will be actually useful and
importantly whether it will be safe so
that's where translational science
animal testing uh and the whole chunk of
moving from Discovery to development
happens so we know there's a whole bunch
of questions that are pretty standard
every Pharma company every biotech
company asks questions like if there's a
model of a disease in a mouse does it
make does this therapy make the mouse
better or not those are useful those are
important but we need new questions new
models we really need new models because
aging isn't a disease that is a or b on
or off one or zero it's a process so we
need to be thinking in some ways
linearly but less statically about
biomarkers about predictive models again
AI can help us ask some of those
questions and maybe even can help us
design organs on a
chip uh so that we can iterate more
cheaply uh in that is this likely to be
safe let's make some predictions let's
when you say organs on a chip are we
talking purely um we map out the way
that a given organ reacts to um given in
chemistry true is that the punchline is
it's basically just pure predictive this
is how a liver works so that that is
actually a pretty useful tool yeah um uh
I think when people talk about organs on
a chip they talk about that they also
talk in a
more physical way
literally taking cells putting them
together and helping them encouraging
them them to interact with each other to
be not just a cell okay a cell we study
it now we're going to make a prediction
about a
human what lies in the middle are groups
of cells cells communicating with each
other cells working together uh that
becomes tissues that become organs that
become people so organ on a chip also is
not just uh a predictive an in silico if
you will computer predictive process
it's also a whole set of approaches
today of taking groups of cells putting
them together and studying them in a
more systems way asking what they can do
as a group uh and putting them to work
to ask questions then about chemistry
and stuff so literally creating mini
organs sometimes called organoids uh and
making them functional to to answer
questions so we can have a model now in
between cells worms and mice actually
model how organs might respond to aging
or therapies that can in that can
interfere with that okay there's
something very very intriguing here let
me ask you do you think we live in a
simulation I'm thinking about this for a
second I am going to say I'm already
surprised I thought you would give me a
shoot from the hip answer that no of
course
not all right here's my
answer one of the things that makes
humans demonstrably different from other
organisms on the planet are we have
Consciousness and we
think that's a good
thing but it gets us in trouble and
partly it gets us in trouble because
thinking outside of your own head is
really hard it's hard personally it's
hard professionally and it's actually
hard scientifically so in that light we
do create by by looking at all the
experiences we've had all the knowledge
we've learned all the things we've
learned from iterating and experimenting
and doing well in jobs and and messing
up in other jobs and and watching other
people do well and mess up uh we we
think we know some truth we say this is
my approach this is my approach to
science this is my approach to
interpreting those data um we've all
heard there's lies damn lies and
statistics well we can convince
ourselves that data is showing us a
bunch of different things and in that
light we are living in our own heads and
we are creating the simulation that we
live in we can't or it's very very hard
to say I'm going to step back from my
round truth assumptions about what this
experiment should show or what that drug
should do and actually be open to
looking at what's really happening
that's super hard uh if we can do it
even a little bit breakthroughs happen
people make breakthroughs in their
careers they make scientific
breakthroughs and insights they invent
new things uh so in that light we are
living in a simulation that we create in
our
heads uh and the interesting thing is
everyone simulation isn't exactly the
same do I believe that there's objective
reality of absolutely I'm a scientist I
believe in objective reality there there
are facts and in that light uh because
if there weren't if we were truly living
in a simulation be probably a lot easier
to develop drugs in The Matrix than in
the real world where biolog is messy and
we don't know everything so uh I don't
think there's a difference so I'm on the
record of having said that we don't live
in a simulation I don't think but I've
said many times what you just said which
is is there really a difference between
being trapped in your own mind and
living in a true objective
simulation uh it is a fact that the
human brain is encased in total darkness
and yet as I look at you it doesn't feel
like that it feels like light is hitting
my brain and I'm simply seeing what is
there versus electromagnetic signals
being processed by my brain and creating
a sense that I'm seeing something but
given that we see
0.35% of the available electromagnetic
spectrum we know that we are
oversimplifying the world grossly and it
becomes a question of okay well if I'm
simplifying it then my brain is making
decisions about what to show me and not
show me it's interpreting what it sees
and what's the interpretation all right
I want to set that aside for a second
and even though I don't know that I
believe this I'm going to make my best
pitch for that we really do live in a
simulation okay uh it goes like this and
the reason that I was thinking about
this is you were talking about Ai and
the complexity of all this and being
able to build
organs in silico that meaning on Silicon
chips it's a fancy way of saying that
it's a computer simulation um so I spend
the vast majority of my time building
video games which is not something
people know much about me yet but they
will if I have anything to do with it uh
and what you begin to realize is you can
create a relatively simple set of
procedural rules and from that is born
an incredible amount of complexity and
so many of the most played video games
and the one I will use have you ever
seen Minecraft yes okay oh I'm I love
this okay uh I've I've got a daughter
I've got nieces amazing so you know the
drill um I have had the Good Fortune of
encountering Minecraft very late in my
life so I don't take it for granted so
when I encountered Minecraft I was like
what on Earth is this incredibly complex
universe that I've stumbled upon where
everybody gets their unique seed and as
you explore the world you realize it's
more and more complicated um I got tired
of being blown up by what are known as
creepers and so I looked up online like
do you keep the creepers away and it was
like put a cat in a boat and I was like
what like that was AI had not seen a cat
and I did not understand why you would
put a cat in a boat anyway what I began
to realize was from a relative I mean
compared to biology it is Minecraft is
stupid simple but from this
incredibly simple set of rules comes an
unimaginable amount of emergent
complexity and as I was playing the game
I realized I was explaining to some of
my teammates how I play and they're like
that's not how most people play
Minecraft and I was like whoa why and so
anyway you begin to realize not only is
there emerging complexity but then the
behaviors of the people engaging with
this simulation also have their own
emergent ways of playing the game that
weren't contemplated when the rules were
set forth in motion now given then that
you can create from procedural rules you
can create something of near infinite
complexity
that to me feels so analogous to the way
that life is and I think the the mistake
that people make when they're assessing
biology is they mistake unknown for
unknowable and I think that biology is
knowable even though it is very
complicated and even though right now we
know so very little and therefore are
able to make so few
predictions as AI becomes more complex
it the reason that AI is so powerful and
the reason that I consider this the
elevator to the peak of Mount Everest is
that what we have not been able to
figure out yet are the patterns that
emerge from the simple set of rules once
we can identify the patterns we can work
backwards to the simple set of rules but
if we can't figure out the patterns
first I mean this is like Newton's Laws
of Motion which then Einstein obviously
refined upon but by discovering simpler
and simpler equations so my hope is that
what AI will be able to do is stop being
tricked by the apparent complexity of
the emergent behavior and it will be
able to ascertain the simple set of
rules that give rise to these patterns
but it has to be able to parse through
these patterns first so when I look at
okay one I want to get back to that the
set of questions that you pose that we
have to be able to ask and answer in
order to truly tame by biology okay so
we have to ask and answer these
questions to really be able to control
biology to do what I think we will be
able to do which
is extend human life
indefinitely now I would like to
introduce for people that don't know the
Dunning Krueger effect so that I people
don't waste time saying that this is Tom
uh in the grips of this which is true by
the way all right the Dunning Krueger
effect is you know so little you think
you know a lot
I completely
acques I know so little it feels like I
know a lot but this is where I think
that we can start to I think that
embracing the Dunning Krueger effect is
the right first step to embarking on a
very complicated journey and I think
that it is actually useful to try to
connect dots that may not connect in the
end and this is something that I look
for in entrepreneurs can you create a
narrative that allows you to have a
direction that you're moving in and at
the same time question your own
narrative because you know it's wrong so
what I'm about to lay out I know is
wrong but it's going to allow me to move
in a direction okay so here are the
questions that I think we have to
answer what causes aging that's question
number
one if we understand what causes aging
then the question becomes can we reset
that process if we can reset that
process then can we solve for
persistence the reason I think
persistence matters is the only reason
that humans care about each other about
themselves is there is a continual sense
of identity so I love my wife my wife
even though she's changing over time and
I'm changing over time we have a sense
of persistence so I have a sense that I
have shared my life with a continual
entity I have a sense that I am a
continual entity and all of that now the
reason that I think that matters is
right now there is an organism on earth
that is truly Immortal meaning unless it
dies a violent death it will never die
and that is this jellyfish the thing is
the
jellyfish to renew its process it has to
basically dedifferentiate all of its
cells back to a Pur poent state so it
basically becomes
a amorphous blob that then reconstitutes
itself back into the jellyfish now I'm
going to guess that if it had memory or
whatever which it probably doesn't but
if it did that would all be wiped out in
that process of becoming Pur potent
again and then reconstituting itself so
that feels like again fully embracing
the Dunning Krueger effect that this is
way too simplistic and we will find over
time that that I'm just not getting
enough into the Nuance but that gives us
something directional to work with with
that what we have to figure out is what
is aging which I think we've covered
which aging is the epig genome beginning
to break down not mutations in DNA but
the way that we bookmark our DNA so that
the cells begin to lose focus and as the
cells begin to lose focus then we would
we age we see all the things we think of
as
aging but to fix that we would have to
remove all of those things which we have
shown uh the yamanaka forget his first
name won the Nobel Prize for showing
that you could bring a cell back to a
Pur potent stage but I have a feeling if
we did that to the whole body that we
would dedifferentiate to the point of
nonsensical like we would cease to be
the same
organism uh and so we have to be able to
solve for that problem if we actually
want one organism to live
forever so uh some great topics to
unpack there
uh in no particular
order you are cor I believe you're
correct can't prove it I believe you're
correct that if we
could become the jellyfish and actually
piece by piece or as as a whole
organism truly reprogram ourselves all
the way back to the beginning we would
this is the metaphysical part I'll get
to the biologic part in a second we
would almost certainly be resetting our
brain which would necessarily reset our
Consciousness which would necessarily
wipe out all those memories and all the
things that we thought of his
life so speaking just for
me look I'm not ready to die I got a lot
left to do in life I got decades I'd
love to live a really long time but am I
willing to say that
sacrificing everything that I've seen
done and felt in life to make my liver
last forever no uh we're humans we're
not jellyfish so that's that's personal
that's
philosophical um I think everyone would
agree with you including myself on the
on the AI part it is a fascinating topic
and applying this tool but also this
approach
to thinking about aging thinking about
drug Discovery thinking about uh
medicine is a fantastic topic one of the
things the reason I call AI a tool and
not sort of the solution it's a tool is
at the end of the
day as far as I know and I don't know
everything AI has to work with the data
set that it's
presented with not anymore they're now
creating synthetic data sets this is one
of the big potential breakthroughs fine
no problem but they are someone
someone's creating the synthetic data
set the AI is creating the synthetic
data set now it's spun off of the
original I I'm going to assert that my
point isn't yet we may get to the part
where my point is vitiated but I'm going
to assume that my Point's still still
valid at the end of the
day the algorithm the
algorithms are working from a set of
ground truths that they have to be
presented with they're not making up
ideas uh
now if and
when algorithms start making up ideas
and saying if that were true then this
might be
true and I'm not sure if it's true
but I wonder if this thing could happen
that's getting closer to what happens
with humans but let's assume for the
moment that at some point at some
fundamental level there's a set of facts
that um are taken as ground truths by
the algorithm to spin up to reduce
complexity to make predictions and even
spin up synthetic data sets what's never
in that world what's never going to go
away is the need to
create more ground truth to actually
make observations to take human to make
living things to take biology and
actually ask questions that yield New
pie