you
this story starts 13 years ago I was a
graduate student in the neurobiology
department here at UCSD and I went into
Student Health one day because I hadn’t
been feeling well and at the end of that
day I went home with the diagnosis of
advanced testicular cancer now normally
this is a terrible thing but in this
case it set me on a path that has
brought me here today so during the
course of my treatment and Memorial
sloan-kettering I realized something
pretty profound most of the medications
that I was taking or derived from nature
now I’m a scientist and have been a
biologist my whole life and I didn’t
know this so I was blown away and I
decided that when I got back to San
Diego I would change the course of my
studies and learn how to do this so when
I got back the administration was very
generous and let me change the focus of
my dissertation so I embarked on this
journey and found an incredible
community here at UCSD that was doing
this work in a very cutting-edge fashion
one of the first things I learned is
that over 65% of all our drugs are
actually derived from nature from
morphine which is derived from the poppy
plant and changed the course of surgery
in the way that we treat pain to aspirin
which was the modified component of the
white willow bark and treats fever and
inflammation
this was known since 400 BC but it
wasn’t until the scientists from Bayer
actually turned it into a drug to
penicillin Alexander Fleming’s discovery
in 1935 when he when he saw a mold
preventing the growth of a bacteria this
change the course of humanity and is
probably a large part of why we’re all
here today and we have Lois satin which
uses human cholesterol fascinating a
microbe a fungus that produces something
that reduces human cholesterol and
finally to tax all the drug that would
eventually save my life is actually
produced by a symbiotic
the Pacific yew tree now why would
compounds produce than these organisms
actually treat human disease I was
fascinated by this and as my graduate
studies continued some remarkable
studies began to emerge regarding the
human microbiome all of these drugs are
produced by microbes so these studies
powered by the advances in genetic
sequencing and in computational power
actually began to show something amazing
the human microbiome is much bigger than
we ever expected it’s actually
outnumbers in cells the human cells by
ten to one genetic composition is
actually a hundred to one versus human
so we are not necessarily humans it’s
changing the way that we think about
health the way that we think about
medicine these microbial populations
have been shown to impact heart disease
obesity immunity cancer and even neural
development this is now standing
discovery but it doesn’t just hold true
in humans it’s actually something that
our planet is covered with in 2009 there
were 20 million estimated species on our
planet that number has changed to
approximately 1 trillion that means that
less than 10 years ago we had
underestimated the vast vast majority of
life less than one one thousandth of 1%
this is less than 10 years ago the
majority of this diversity of life is
actually microbial so this is a new tree
of life that captures that diversity
over here in the corner are humans
right next to humans our amoeba
everything else is microbial this is
amazing this means that everything that
we normally associate with life and with
evolution sort of lies between two
points no wings no scales no venom the
rest of this diversity just relies on
chemistry this is the language of life
and the source of these medicines as you
can imagine these medicines are actually
much more complex than anything we make
synthetically take Levesque this is
something produced by humans and is kind
of a pinnacle of humans synthetic
chemistry it was designed by scientists
to fit a specific receptor in cancer and
by all measures is a very successful
drug take rapamycin this is something
discovered on Easter Island in 1975 as
an antifungal agent this antifungal was
soon discovered to be an incredible
immunosuppressive as well as an
anti-cancer agent what’s remarkable is
that this is actually the first molecule
ever to have statistically shown to
extend mammalian life this molecule
extends life and is currently in
clinical trials for dogs for just that
this chemical diversity is fascinating
this language of life that we don’t
understand yet is the source of many new
therapeutics one of those places that is
just tremendously under studied is the
ocean this is Halla Condren be a
molecule produced by a sponge the right
half of it is actually a successful
cancer therapeutic it prevents cell
division in a novel way but we don’t
know what the rest of this molecule is
actually doing another way to think
about synthetic versus natural
naturally-occurring chemistry is to plot
it in space this is what synthetic
chemistry looks like with the
distribution of these compounds
representing chemical diversity they
type more tightly clustered they
are the more similar so this is
synthetic chemistry naturally-occurring
chemistry much more broadly so I left
graduate school with these ideas and I
was hoping that I would be able to
somehow harness this chemical language
this chemical diversity to more
efficiently yield new breakthrough
therapeutics and with the hypothesis
that if we started with a tremendous
chemical library this chemical diversity
this language and we tested it
repeatedly across different diseases
over and over again it would yield a
tremendous dataset and if you use this
data set and combine it with the modern
computational power AI machine learning
deep data mining we would be able to
yield better new therapeutics like ever
before so over the last five years with
an incredible team of young scientists
and entrepreneurs we’ve launched this
effort and actually validated this
approach starting with the ocean
we’ve been all over the world collecting
amazing samples this is us in Curacao
with Fabien Cousteau we talked our way
onto the sub and we brought up these
sponges which are now part of a
medicinal chemistry collection we go
back to our sample of chemical space
what we’re doing is actually expanding
it right we’re making it bigger we’re
expanding the possibilities for drugs
and so one of the approaches that we use
to start mining it is something
developed here at UCSD called molecular
networking so molecular networking
allows you to see the similarities
between all of these dots each of these
dots represents a molecule and instead
of finding a needle in a haystack it’s
really treating each dot as a needle or
perhaps a key that has a lock and so
this approach actually allows us to see
the similarities between these keys and
the possibility that they’ll work on
several locks or on which locks they
might work and then as we overlay
disease results as we test in parasitic
cancer
immune immunity we can begin to ask
which of these dots is actually useful
for let’s say rapidly dividing cancer
cells and this is the first place that
we pointed this approach and the first
molecule that came out is actually
currently part of a targeted cancer
therapeutic that’s about to enter
clinical trials
hopefully the most recent area that
we’ve been pointing this is immune
modulation can we find something that
actually modulates the human immune
system to treat cancer better or to
treat infection or to prevent autoimmune
disease but really my favorite story is
about malaria this is work that we’ve
done with the Bill and Melinda Gates
Foundation over the last two years now
malaria is something we don’t think
about a lot here but it affects over 200
million people each year with the
majority of them in sub-saharan Africa
and it kills a thousand children a day
so we started digging into our big nest
of opportunity and quickly found
something in less than four months that
actually treats malaria perhaps in a
totally new way incredibly potent and is
currently being evaluated further here
at UCSD so the reason that this is my
favorite story is that if you think
about where we collected this organism
it was the Atacama Desert
we found this algae growing the Atacama
Desert brought it back processed that
tested it and found this thing that was
present and less less concentration than
uranium is found in salt water so it was
tiny abundance this was remarkable but
when we looked in our data we found it
in 25 different hosts from across the
planet just this tiny tiny presence of
this incredibly potent anti-parasitic
agent from all over the world so as we
think about our planet we think about
diversity
I urge you to think about the potential
that lays out there and how little we
understand about life and about this
language that is all around us our
microbiome ties us to our communities to
ourselves to our neighbors those
communities are tied to our ecosystems
and those ecosystems are tied to our
planet
thread lightly thank you
[Applause]
this story starts 13 years ago I was a
graduate student in the neurobiology
department here at UCSD and I went into
Student Health one day because I hadn’t
been feeling well and at the end of that
day I went home with the diagnosis of
advanced testicular cancer now normally
this is a terrible thing but in this
case it set me on a path that has
brought me here today so during the
course of my treatment and Memorial
sloan-kettering I realized something
pretty profound most of the medications
that I was taking or derived from nature
now I’m a scientist and have been a
biologist my whole life and I didn’t
know this so I was blown away and I
decided that when I got back to San
Diego I would change the course of my
studies and learn how to do this so when
I got back the administration was very
generous and let me change the focus of
my dissertation so I embarked on this
journey and found an incredible
community here at UCSD that was doing
this work in a very cutting-edge fashion
one of the first things I learned is
that over 65% of all our drugs are
actually derived from nature from
morphine which is derived from the poppy
plant and changed the course of surgery
in the way that we treat pain to aspirin
which was the modified component of the
white willow bark and treats fever and
inflammation
this was known since 400 BC but it
wasn’t until the scientists from Bayer
actually turned it into a drug to
penicillin Alexander Fleming’s discovery
in 1935 when he when he saw a mold
preventing the growth of a bacteria this
change the course of humanity and is
probably a large part of why we’re all
here today and we have Lois satin which
uses human cholesterol fascinating a
microbe a fungus that produces something
that reduces human cholesterol and
finally to tax all the drug that would
eventually save my life is actually
produced by a symbiotic
the Pacific yew tree now why would
compounds produce than these organisms
actually treat human disease I was
fascinated by this and as my graduate
studies continued some remarkable
studies began to emerge regarding the
human microbiome all of these drugs are
produced by microbes so these studies
powered by the advances in genetic
sequencing and in computational power
actually began to show something amazing
the human microbiome is much bigger than
we ever expected it’s actually
outnumbers in cells the human cells by
ten to one genetic composition is
actually a hundred to one versus human
so we are not necessarily humans it’s
changing the way that we think about
health the way that we think about
medicine these microbial populations
have been shown to impact heart disease
obesity immunity cancer and even neural
development this is now standing
discovery but it doesn’t just hold true
in humans it’s actually something that
our planet is covered with in 2009 there
were 20 million estimated species on our
planet that number has changed to
approximately 1 trillion that means that
less than 10 years ago we had
underestimated the vast vast majority of
life less than one one thousandth of 1%
this is less than 10 years ago the
majority of this diversity of life is
actually microbial so this is a new tree
of life that captures that diversity
over here in the corner are humans
right next to humans our amoeba
everything else is microbial this is
amazing this means that everything that
we normally associate with life and with
evolution sort of lies between two
points no wings no scales no venom the
rest of this diversity just relies on
chemistry this is the language of life
and the source of these medicines as you
can imagine these medicines are actually
much more complex than anything we make
synthetically take Levesque this is
something produced by humans and is kind
of a pinnacle of humans synthetic
chemistry it was designed by scientists
to fit a specific receptor in cancer and
by all measures is a very successful
drug take rapamycin this is something
discovered on Easter Island in 1975 as
an antifungal agent this antifungal was
soon discovered to be an incredible
immunosuppressive as well as an
anti-cancer agent what’s remarkable is
that this is actually the first molecule
ever to have statistically shown to
extend mammalian life this molecule
extends life and is currently in
clinical trials for dogs for just that
this chemical diversity is fascinating
this language of life that we don’t
understand yet is the source of many new
therapeutics one of those places that is
just tremendously under studied is the
ocean this is Halla Condren be a
molecule produced by a sponge the right
half of it is actually a successful
cancer therapeutic it prevents cell
division in a novel way but we don’t
know what the rest of this molecule is
actually doing another way to think
about synthetic versus natural
naturally-occurring chemistry is to plot
it in space this is what synthetic
chemistry looks like with the
distribution of these compounds
representing chemical diversity they
type more tightly clustered they
are the more similar so this is
synthetic chemistry naturally-occurring
chemistry much more broadly so I left
graduate school with these ideas and I
was hoping that I would be able to
somehow harness this chemical language
this chemical diversity to more
efficiently yield new breakthrough
therapeutics and with the hypothesis
that if we started with a tremendous
chemical library this chemical diversity
this language and we tested it
repeatedly across different diseases
over and over again it would yield a
tremendous dataset and if you use this
data set and combine it with the modern
computational power AI machine learning
deep data mining we would be able to
yield better new therapeutics like ever
before so over the last five years with
an incredible team of young scientists
and entrepreneurs we’ve launched this
effort and actually validated this
approach starting with the ocean
we’ve been all over the world collecting
amazing samples this is us in Curacao
with Fabien Cousteau we talked our way
onto the sub and we brought up these
sponges which are now part of a
medicinal chemistry collection we go
back to our sample of chemical space
what we’re doing is actually expanding
it right we’re making it bigger we’re
expanding the possibilities for drugs
and so one of the approaches that we use
to start mining it is something
developed here at UCSD called molecular
networking so molecular networking
allows you to see the similarities
between all of these dots each of these
dots represents a molecule and instead
of finding a needle in a haystack it’s
really treating each dot as a needle or
perhaps a key that has a lock and so
this approach actually allows us to see
the similarities between these keys and
the possibility that they’ll work on
several locks or on which locks they
might work and then as we overlay
disease results as we test in parasitic
cancer
immune immunity we can begin to ask
which of these dots is actually useful
for let’s say rapidly dividing cancer
cells and this is the first place that
we pointed this approach and the first
molecule that came out is actually
currently part of a targeted cancer
therapeutic that’s about to enter
clinical trials
hopefully the most recent area that
we’ve been pointing this is immune
modulation can we find something that
actually modulates the human immune
system to treat cancer better or to
treat infection or to prevent autoimmune
disease but really my favorite story is
about malaria this is work that we’ve
done with the Bill and Melinda Gates
Foundation over the last two years now
malaria is something we don’t think
about a lot here but it affects over 200
million people each year with the
majority of them in sub-saharan Africa
and it kills a thousand children a day
so we started digging into our big nest
of opportunity and quickly found
something in less than four months that
actually treats malaria perhaps in a
totally new way incredibly potent and is
currently being evaluated further here
at UCSD so the reason that this is my
favorite story is that if you think
about where we collected this organism
it was the Atacama Desert
we found this algae growing the Atacama
Desert brought it back processed that
tested it and found this thing that was
present and less less concentration than
uranium is found in salt water so it was
tiny abundance this was remarkable but
when we looked in our data we found it
in 25 different hosts from across the
planet just this tiny tiny presence of
this incredibly potent anti-parasitic
agent from all over the world so as we
think about our planet we think about
diversity
I urge you to think about the potential
that lays out there and how little we
understand about life and about this
language that is all around us our
microbiome ties us to our communities to
ourselves to our neighbors those
communities are tied to our ecosystems
and those ecosystems are tied to our
planet
thread lightly thank you
[Applause]
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