you
for the last several years my lab has
been focused in a pursuit it’s to use
the power of genomic science and human
partnership to head off
emerging diseases before they become
global pandemics so in the last part of
the 20th century emerging diseases began
to come up out of nowhere
so in 1967 Marburg virus appeared in
1969 Lassa virus in 1976 Ebola and in
the 1980’s HIV and people attributed
this to increasing world’s population
globalization changing climates and our
increased encroachment into animal
habitats and in 1990 the Institute of
Medicine created a report a landmark
report called emerging infections
microbial threats to health in the
United States in which they coined the
term emerging disease and over time this
is taken off the report listed many many
microbes that they considered emerging
these were microbes that they believed
were been new to human populations or
rare in the population that were
beginning to rise in prevalence and with
the help of popular media we started to
think about this all in the collective
conscious with terms like outbreak or
contagion they sound familiar or
pandemic in the way that we think about
them are monkeys deep in the forest
workers in the Far East with animal
products reports going round the world
and we imagine a scene that looks like
this where there’s clinical workers and
full protective gear a village up in
arms a dramatic scene that’s very clear
what’s going on but our labs since begun
to think that the true view of an
emerging disease looks more like this
which is a quiet village a sleeping
mother and her child within a storm
brewing inside going undetected and the
way I started thinking about this the
way my own ideas about this began
brewing were not out in the field it was
actually back at the Broad Institute in
Cambridge Massachusetts where we have
one of the largest genome centers in the
world and we’re generating data from
genomes analyzing them thousands
millions billions of letters
that make up the genomes of us and other
species and the data the pictures look
like this strings and strings of letters
in which we’re trying to interpret and
the amazing thing about these letters is
that they code what make us and within
them hide the secrets of who we are and
how we adapt and so when a new variant
emerges in a population and it enhances
the ability for one to survive and
reproduce and pass on those those that
mutation it’ll spread very quickly
through the population and when it does
it leaves behind a footprint a footprint
that we can trace to help us track down
what that change was what it did and get
clues to our survival and the amazing
thing is that you can do this by just
looking at a hundred people living today
if you analyze a population with just
that many people even fewer and you look
at the DNA within them there’s actually
an archaeological record that’s hidden
in our DNA that can tell you about our
history and you can begin to see these
variants that have spread through the
population and understand what they did
and our our lab develops these methods
that go by and look for those things and
the methods used to be quite coarse what
we could do is we could see these
different regions of the genome that
were important but they were very sort
of course signals with thousands of
different variants within them we were
trying to figure out which was the one
that was important that was driving
something meaningful and recently we had
a breakthrough we got much better at
localizing where the signal is coming
from and trying to understand what had
happened and some of the things that we
find are ones that you would expect or
at least that sort of are in line with
our now picture of human evolution which
were things like changing skin colour as
we moved out of Africa into regions that
had lower light the ability to drink
milk and digest milk into adulthood as
we domesticated cattle changes in our
red blood cell that protects them from
the parasite malaria but we have found
hundreds of these candidates and we can
only explain a handful and so there are
many other candidates each one tells a
story that we can pursue to understand
the key to human survival and one that
sort of attracted my attention was a
gene called large which was critical and
under very strong selection
in a population of Yoruba ethnicity from
Nigeria and so I went to see what is the
gene to and how is it acting and as it
turns out it has many functions but one
of its key functions is it’s critical
for the entry of a virus called Lassa
virus so what it does is actually this
gene large modifies the receptor for
lots of virus the key in which the virus
can get into the cell without this
modification this change the virus can
enter and so I wondered whether or not
seeing this very strong signal of
adaptation at this gene in this
population whether or not it had
something to do with this virus and the
disease that the virus causes lots of
fever but that seemed a bit unlikely
because I had gone to medical school and
I’d never even heard of
lots of fever and I went back and I
looked in my microbiology textbook and
it’s just a footnote there lots of virus
one of the arena viruses but very sort
of very not very well known definitely
not compared to other viruses like Ebola
so how could it be having such an impact
so I’m going to tell you a little bit
about the disease and just want to warn
you that the next slide just for a few
seconds is going to show us a picture
that’s a little unsettling so Lassa
fever causes a hemorrhagic fever it’s a
very deadly disease it can travel
through the air and it can have fatality
rates that exceed 50 percent and so it
is part of a small set of agents called
biosafety level 4 like Ebola like marled
lurk like smallpox these agents who pose
a very great individual risk as well as
a global risk but unlike what we think
about many of these diseases last is
actually known to be quite widespread
and interestingly it’s very common in
West Africa and common in Nigeria where
we identified this signal of adaptation
and so we set out there to figure out
whether or not there might be genetic
resistance that may have emerged through
this virus being present in that
population and so we went to Rouen
Nigeria so the Aruba specialist teaching
hospital is a hospital in a rural part
of Nigeria where we set out with
collaborators in Germany to begin to
study their Kenema government hospital
we partnered with Tulane University who
had set up a facility there to study in
rural Sierra Leone and in order to begin
to do this kind of work just to begin
to research the first thing you need to
do is understand the space there are
clinicians that have been working for
many many years treating this disease
and working very hard and so we
partnered with them and what we did is
we brought Diagnostics genomic tests to
test for the viruses presence and you
know in order to basically enroll
individuals into our study and begin to
look at it but obviously to do epical
research we have to make sure that all
of the patients have the standard of
care so we also ensured that a treatment
at ribavirin was present and that
treatment actually has been shown to
reduce the fatality from 55% to 5% but
only if given within the first few days
of infection at a time when by clinical
symptoms it’s really hard to pick up
that that’s what you have and so we had
done this to set the foundations for our
work but were surprised by the impact
and the and sort of the the amazing
impact that exceeded our expectations is
that you know as we implemented
diagnostics and therapies in these sites
survival started to increase the
population became engaged and the
doctors became empowered and a couple of
stories that the hospital likes to talk
about is before we had started there
they used to lose they would say three
to five physicians and staff each year
in the course of treating Lassa fever
but since we instituted this and the
policies around it they haven’t lost the
staff yet I’m going to knock on wood for
that one and also you know women a
pregnant women in there and their
children had the highest fatality rates
and they began to survive and succeed
and so we began to get people coming
from further and further away from
hundreds of kilometers to the hospital
and we saw many lots of fever patients
and again just for one moment I’m going
to show that slide of the classic lots
of fever patient that looks like this
and we have many of those unfortunately
but we also see a large number of people
that look like this seemingly innocuous
but testing positive for Lassa virus and
just as likely to be fatal
and so we began to think these are the
undetected the individuals who we don’t
know are harboring these diseases and so
the question that we came to is is this
actually emerging disease that we’re
talking about here are we talking about
emerging diagnosis of diseases that have
been with us all along this picture
year was designed by Steven Geyer who’s
the first author of a paper with the
same title that we published and Steven
is not just a scientist but an artist he
was flying over the Congo River where
out of his airplane he took a picture of
the river is very close to where Ebola
was first discovered and as an artist he
transformed the river into the shape of
the Ebola virus we published this with
the paper to give a sense of if we
looked from a different angle would we
recognize that these viruses are present
and have been with us all along and the
data at least for Lassa fever suggests
that that’s the case so we went back and
we looked and in fact actually there’s a
test antibody test that can tell you
whether or not you’ve had evidence of
having a disease before being infected
with a virus and in fact in some
populations Nigeria Sierra Leone Liberia
Guinea over 20% of population of
evidence millions of people of evidence
of been exposed philosophers and it
would make sense that there is such
exposure because that rodent master news
gnat Olympus has developed the ability
to harbor this virus in its blood
continually and it’s spread throughout
West Africa and even throughout
sub-saharan Africa and we sequence the
virus from Nigeria and Sierra Leone and
we can use genomic dating technologies
to say how long has the virus been
around and we dated the mutation and to
have emerged and to have been
circulating within Nigeria for over a
thousand years I’m spreading out
throughout West Africa so why now we’re
not looking at what’s an emerging
disease we’re looking at a virus that is
circulating widely and has been with us
for over millennia and the data I won’t
show here for Ebola suggests a very
similar pattern so this is these
diseases are here and we can tackle them
and how does that affect Public Health
the way we think about it so you know
this is a circle that we talked about we
had started the Broad Institute and
we’re setting out to study this virus in
order to do so we had to bring
Diagnostics to test for it and we were
so successful that the community became
engaged and the doctors became empowered
and we started to get people for coming
from hundreds of kilometres and we’re
able to identify many people with lots
of virus but the vast majority of the
people we were looking at has something
we don’t know that we they didn’t test
for the common things like malaria and
laso that we were testing there and so
as
we have it we had all of these different
samples we’ve sent them back to the
United States and we’re identifying all
sorts of new things that are infecting
these individuals and the idea is that
we are going to take those back and
create new Diagnostics that incorporate
all of these viruses that are
circulating and empower the population
once again and it creates this positive
loop that rather than going and asking
people to help with research we’re
asking them to do surveillance we’re
connecting with them working together to
create this local to enhance the local
community and to also enhance the global
population creating this positive loop
and that’s what we work to and this is
where it brings us to collaboration you
can’t study a disease as lethal and
devastating as Lassa fever without
complete trust and the people that you
work with and respect for them and I
have the most amazing group of
individuals I work with my students in
my lab my collaborators in Africa and
around the world they’re exceptional
people that are on the front lines of a
devastating disease
seeing people die every day but working
and working and we are all severely
infected so this is a t-shirt that I’m
wearing that my amazing and creative lab
created it says I’m severely infected by
science and in the back it says science
is infectious and it really is it’s
extraordinary I said the way that
science brings people together working
together towards a common cause – its
tackling these emerging diseases before
they become global pandemics these are
the amazing women of the Arroyo
specialist teaching hospital where I
work they’re not only brilliant and kind
but they have beautiful voices and I
discovered this when I was on a long
trip to Nigeria I’d brought my travel
guitar along with me and I was after
work one day playing one of the songs
for my alternative rock song for my band
and they started harmonizing and it was
amazing I was just overwhelmed and I was
so excited that I went recorded the song
with them an acoustic version of the
song and the song essentially is called
headlight waves and the idea behind it
is it talks about the greed and jealousy
and destruction in the world and
darkness but as the lyrics go it says
hold on it won’t be long hold on
cuz I know you come like waves into this
dark and light you light the way and all
of the ways that they fade you shine
come live
laughing
and
I want to thank National Geographic for
working for the last 125 years to try to
preserve the planet and thank you for
allowing me to participate in this
journey we do this for each other and
for Lassa fever patients thank
you
for the last several years my lab has
been focused in a pursuit it’s to use
the power of genomic science and human
partnership to head off
emerging diseases before they become
global pandemics so in the last part of
the 20th century emerging diseases began
to come up out of nowhere
so in 1967 Marburg virus appeared in
1969 Lassa virus in 1976 Ebola and in
the 1980’s HIV and people attributed
this to increasing world’s population
globalization changing climates and our
increased encroachment into animal
habitats and in 1990 the Institute of
Medicine created a report a landmark
report called emerging infections
microbial threats to health in the
United States in which they coined the
term emerging disease and over time this
is taken off the report listed many many
microbes that they considered emerging
these were microbes that they believed
were been new to human populations or
rare in the population that were
beginning to rise in prevalence and with
the help of popular media we started to
think about this all in the collective
conscious with terms like outbreak or
contagion they sound familiar or
pandemic in the way that we think about
them are monkeys deep in the forest
workers in the Far East with animal
products reports going round the world
and we imagine a scene that looks like
this where there’s clinical workers and
full protective gear a village up in
arms a dramatic scene that’s very clear
what’s going on but our labs since begun
to think that the true view of an
emerging disease looks more like this
which is a quiet village a sleeping
mother and her child within a storm
brewing inside going undetected and the
way I started thinking about this the
way my own ideas about this began
brewing were not out in the field it was
actually back at the Broad Institute in
Cambridge Massachusetts where we have
one of the largest genome centers in the
world and we’re generating data from
genomes analyzing them thousands
millions billions of letters
that make up the genomes of us and other
species and the data the pictures look
like this strings and strings of letters
in which we’re trying to interpret and
the amazing thing about these letters is
that they code what make us and within
them hide the secrets of who we are and
how we adapt and so when a new variant
emerges in a population and it enhances
the ability for one to survive and
reproduce and pass on those those that
mutation it’ll spread very quickly
through the population and when it does
it leaves behind a footprint a footprint
that we can trace to help us track down
what that change was what it did and get
clues to our survival and the amazing
thing is that you can do this by just
looking at a hundred people living today
if you analyze a population with just
that many people even fewer and you look
at the DNA within them there’s actually
an archaeological record that’s hidden
in our DNA that can tell you about our
history and you can begin to see these
variants that have spread through the
population and understand what they did
and our our lab develops these methods
that go by and look for those things and
the methods used to be quite coarse what
we could do is we could see these
different regions of the genome that
were important but they were very sort
of course signals with thousands of
different variants within them we were
trying to figure out which was the one
that was important that was driving
something meaningful and recently we had
a breakthrough we got much better at
localizing where the signal is coming
from and trying to understand what had
happened and some of the things that we
find are ones that you would expect or
at least that sort of are in line with
our now picture of human evolution which
were things like changing skin colour as
we moved out of Africa into regions that
had lower light the ability to drink
milk and digest milk into adulthood as
we domesticated cattle changes in our
red blood cell that protects them from
the parasite malaria but we have found
hundreds of these candidates and we can
only explain a handful and so there are
many other candidates each one tells a
story that we can pursue to understand
the key to human survival and one that
sort of attracted my attention was a
gene called large which was critical and
under very strong selection
in a population of Yoruba ethnicity from
Nigeria and so I went to see what is the
gene to and how is it acting and as it
turns out it has many functions but one
of its key functions is it’s critical
for the entry of a virus called Lassa
virus so what it does is actually this
gene large modifies the receptor for
lots of virus the key in which the virus
can get into the cell without this
modification this change the virus can
enter and so I wondered whether or not
seeing this very strong signal of
adaptation at this gene in this
population whether or not it had
something to do with this virus and the
disease that the virus causes lots of
fever but that seemed a bit unlikely
because I had gone to medical school and
I’d never even heard of
lots of fever and I went back and I
looked in my microbiology textbook and
it’s just a footnote there lots of virus
one of the arena viruses but very sort
of very not very well known definitely
not compared to other viruses like Ebola
so how could it be having such an impact
so I’m going to tell you a little bit
about the disease and just want to warn
you that the next slide just for a few
seconds is going to show us a picture
that’s a little unsettling so Lassa
fever causes a hemorrhagic fever it’s a
very deadly disease it can travel
through the air and it can have fatality
rates that exceed 50 percent and so it
is part of a small set of agents called
biosafety level 4 like Ebola like marled
lurk like smallpox these agents who pose
a very great individual risk as well as
a global risk but unlike what we think
about many of these diseases last is
actually known to be quite widespread
and interestingly it’s very common in
West Africa and common in Nigeria where
we identified this signal of adaptation
and so we set out there to figure out
whether or not there might be genetic
resistance that may have emerged through
this virus being present in that
population and so we went to Rouen
Nigeria so the Aruba specialist teaching
hospital is a hospital in a rural part
of Nigeria where we set out with
collaborators in Germany to begin to
study their Kenema government hospital
we partnered with Tulane University who
had set up a facility there to study in
rural Sierra Leone and in order to begin
to do this kind of work just to begin
to research the first thing you need to
do is understand the space there are
clinicians that have been working for
many many years treating this disease
and working very hard and so we
partnered with them and what we did is
we brought Diagnostics genomic tests to
test for the viruses presence and you
know in order to basically enroll
individuals into our study and begin to
look at it but obviously to do epical
research we have to make sure that all
of the patients have the standard of
care so we also ensured that a treatment
at ribavirin was present and that
treatment actually has been shown to
reduce the fatality from 55% to 5% but
only if given within the first few days
of infection at a time when by clinical
symptoms it’s really hard to pick up
that that’s what you have and so we had
done this to set the foundations for our
work but were surprised by the impact
and the and sort of the the amazing
impact that exceeded our expectations is
that you know as we implemented
diagnostics and therapies in these sites
survival started to increase the
population became engaged and the
doctors became empowered and a couple of
stories that the hospital likes to talk
about is before we had started there
they used to lose they would say three
to five physicians and staff each year
in the course of treating Lassa fever
but since we instituted this and the
policies around it they haven’t lost the
staff yet I’m going to knock on wood for
that one and also you know women a
pregnant women in there and their
children had the highest fatality rates
and they began to survive and succeed
and so we began to get people coming
from further and further away from
hundreds of kilometers to the hospital
and we saw many lots of fever patients
and again just for one moment I’m going
to show that slide of the classic lots
of fever patient that looks like this
and we have many of those unfortunately
but we also see a large number of people
that look like this seemingly innocuous
but testing positive for Lassa virus and
just as likely to be fatal
and so we began to think these are the
undetected the individuals who we don’t
know are harboring these diseases and so
the question that we came to is is this
actually emerging disease that we’re
talking about here are we talking about
emerging diagnosis of diseases that have
been with us all along this picture
year was designed by Steven Geyer who’s
the first author of a paper with the
same title that we published and Steven
is not just a scientist but an artist he
was flying over the Congo River where
out of his airplane he took a picture of
the river is very close to where Ebola
was first discovered and as an artist he
transformed the river into the shape of
the Ebola virus we published this with
the paper to give a sense of if we
looked from a different angle would we
recognize that these viruses are present
and have been with us all along and the
data at least for Lassa fever suggests
that that’s the case so we went back and
we looked and in fact actually there’s a
test antibody test that can tell you
whether or not you’ve had evidence of
having a disease before being infected
with a virus and in fact in some
populations Nigeria Sierra Leone Liberia
Guinea over 20% of population of
evidence millions of people of evidence
of been exposed philosophers and it
would make sense that there is such
exposure because that rodent master news
gnat Olympus has developed the ability
to harbor this virus in its blood
continually and it’s spread throughout
West Africa and even throughout
sub-saharan Africa and we sequence the
virus from Nigeria and Sierra Leone and
we can use genomic dating technologies
to say how long has the virus been
around and we dated the mutation and to
have emerged and to have been
circulating within Nigeria for over a
thousand years I’m spreading out
throughout West Africa so why now we’re
not looking at what’s an emerging
disease we’re looking at a virus that is
circulating widely and has been with us
for over millennia and the data I won’t
show here for Ebola suggests a very
similar pattern so this is these
diseases are here and we can tackle them
and how does that affect Public Health
the way we think about it so you know
this is a circle that we talked about we
had started the Broad Institute and
we’re setting out to study this virus in
order to do so we had to bring
Diagnostics to test for it and we were
so successful that the community became
engaged and the doctors became empowered
and we started to get people for coming
from hundreds of kilometres and we’re
able to identify many people with lots
of virus but the vast majority of the
people we were looking at has something
we don’t know that we they didn’t test
for the common things like malaria and
laso that we were testing there and so
as
we have it we had all of these different
samples we’ve sent them back to the
United States and we’re identifying all
sorts of new things that are infecting
these individuals and the idea is that
we are going to take those back and
create new Diagnostics that incorporate
all of these viruses that are
circulating and empower the population
once again and it creates this positive
loop that rather than going and asking
people to help with research we’re
asking them to do surveillance we’re
connecting with them working together to
create this local to enhance the local
community and to also enhance the global
population creating this positive loop
and that’s what we work to and this is
where it brings us to collaboration you
can’t study a disease as lethal and
devastating as Lassa fever without
complete trust and the people that you
work with and respect for them and I
have the most amazing group of
individuals I work with my students in
my lab my collaborators in Africa and
around the world they’re exceptional
people that are on the front lines of a
devastating disease
seeing people die every day but working
and working and we are all severely
infected so this is a t-shirt that I’m
wearing that my amazing and creative lab
created it says I’m severely infected by
science and in the back it says science
is infectious and it really is it’s
extraordinary I said the way that
science brings people together working
together towards a common cause – its
tackling these emerging diseases before
they become global pandemics these are
the amazing women of the Arroyo
specialist teaching hospital where I
work they’re not only brilliant and kind
but they have beautiful voices and I
discovered this when I was on a long
trip to Nigeria I’d brought my travel
guitar along with me and I was after
work one day playing one of the songs
for my alternative rock song for my band
and they started harmonizing and it was
amazing I was just overwhelmed and I was
so excited that I went recorded the song
with them an acoustic version of the
song and the song essentially is called
headlight waves and the idea behind it
is it talks about the greed and jealousy
and destruction in the world and
darkness but as the lyrics go it says
hold on it won’t be long hold on
cuz I know you come like waves into this
dark and light you light the way and all
of the ways that they fade you shine
come live
laughing
and
I want to thank National Geographic for
working for the last 125 years to try to
preserve the planet and thank you for
allowing me to participate in this
journey we do this for each other and
for Lassa fever patients thank
you
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