We need better drugs now Francis Collins
Tony asked for a show of hands how many
people here are over the age of 48 well
there do seem to be a few well
congratulations because if you look at
this particular slide of us life
expectancy you are now in excess of the
average lifespan of somebody who was
born in 1900 but look what happened in
the course of that century if you follow
that curve you’ll see that it starts way
down there there’s that dip there for
the 1918 flu and here we are at 2010
average life expectancy of a child born
today aged 79 and we are not done yet
that’s the good news but there’s still a
lot of work to do so for instance if you
ask how many diseases do we now know the
exact molecular basis turns out it’s
about 4000 which is pretty amazing
because most of those molecular
discoveries have just happened in the
last little while it’s exciting to see
that in terms of what we’ve learned but
how many of those 4,000 diseases now
have treatments available only about 250
so we have this huge challenge this huge
gap you would think this wouldn’t be too
hard that we would simply have the
ability to take this fundamental
information that we’re learning about
how it is that basic biology teaches us
about the causes of disease and build a
bridge across this yawning gap between
what we’ve learned about basic science
and its application a bridge that would
look maybe something like this where
you’d have to put together a nice shiny
way to get from one side to the other
what would it be nice if it was that
easy unfortunately it’s not in reality
trying to go from fundamental knowledge
to its application is more like this
there are no shiny bridges you sort of
place your bets maybe you’ve got a
swimmer in our rowboat and i’ve sailboat
in a tugboat and you set them off on
their way and the rains come and the
lightning flashes and oh my gosh there’s
sharks in the water and the swimmer gets
into trouble and the swimmer drowned and
you know the sail boat capsized
and that tugboat well it hit the rocks
and maybe if you’re lucky somebody gets
across well what does this really look
like well what is it to make a
therapeutic anyway what’s a drug a drug
is made up of a small molecule of
hydrogen carbon oxygen nitrogen and a
few other atoms all cobbled together in
a shape and it’s those shapes that
determine whether in fact that
particular drug is going to hit its
target is it going to land where it’s
supposed to so look at this picture here
a lot of shapes dancing around for you
now what you need to do if you’re trying
to develop a new treatment for autism or
Alzheimer’s disease or cancer is to find
the right shape in that mix that will
ultimately provide benefit and will be
safe and when you look at what happens
to that pipeline you start out maybe
with thousands tens of thousands of
compounds you weed down through various
steps that cause many of these to fail
ultimately maybe you can run a clinical
trial with four or five of these and if
all goes well 14 years after you started
you will get one approval and it will
cost you upwards of a billion dollars
for that one success so we have to look
at this pipeline the way an engineer
would and say how can we do better and
that’s the main theme of what I want to
say to you this morning how can we make
this go faster how can we make it more
successful well let me tell you about a
few examples where this has actually
worked the one that has just happened in
this last a few months is the successful
approval of a drug for cystic fibrosis
but it’s taking a long time to get there
cystic fibrosis had its molecular cause
discovered in 1989 by my group working
with another group in Toronto
discovering what the mutation was in a
particular gene on chromosome 7 that
picture you see there here it is that’s
the same kid that’s Danny Bessette 23
years later because this is the year and
it’s also the year where Danny got
married where we have for the first time
the approval by the FDA of a drug that
precisely targets the defect in cystic
fibrosis based upon all this molecular
understanding that’s the good news the
bad news is this drug doesn’t actually
treat all cases of cystic fibrosis and
it won’t work for Danny and we’re still
waiting for that next generation to help
him but it took 23 years to get this far
that’s too long how do we go faster
well more money to go faster is to take
advantage of
technology and a very important
technology that we depend on for all of
this it’s the human genome the ability
to be able to look at a chromosome to
unzip it to pull out all the DNA and to
be able to then read out the letters in
that DNA code the a C’s GS and T’s that
are our instruction book in the
instruction book for all living things
and the cost of doing this which used to
be in the hundreds of millions of
dollars has in the course of the last 10
years fallen faster than Moore’s law
down to the point where it is less than
ten thousand dollars today to have your
genome sequenced or mine and we’re
headed for the thousand dollar genome
fairly soon well that’s exciting how
does that play out in terms of
application to a disease I want to tell
you about another disorder this one is a
disorder which is quite rare
it’s called hutchinson gilford progeria
and it is the most dramatic form of
premature aging only about one in every
four million kids has this disease and
in a simple way what happens is because
of a mutation in a particular gene a
protein is made that’s toxic to the cell
and it causes these individuals to age
at about seven times the normal rate let
me show you a video of what that does to
the cell the normal cell if you looked
at it under the microscope would have a
nucleus sitting in the middle of the
cell which is nice and round and smooth
in its boundaries and it looks kind of
like that a progeria cell on the other
hand because of this toxic protein
called progeria has these lumps and
bumps in it so what we would like to do
after discovering this back in 2003 is
to come up with a way to try to correct
that
well again by knowing something about
the molecular pathways it was possible
to pick one of those many many compounds
that might have been useful and try it
out in a named experiment done in cell
culture and shown here in a cartoon if
you take that particular compound and
you add it to that cell that has
progeria and you watch to see what
happened in just 72 hours that cell
becomes for all purposes that we can
determine almost like a normal cell well
that was exciting but would it actually
work in a real human being
this is led in the space
of only four years from the time the
gene was discovered to the start of a
clinical trial to a test of that very
compound and the kids that you see here
all volunteered to be part of this 28 of
them and you can see as soon as the
picture comes up that they are in fact a
remarkable group of young people all
afflicted by this disease all looking
quite similar to each other and instead
of telling you more about it I’m going
to invite one of them Sam burns from
Boston who’s here this morning to come
up on the stage and tell us about his
experience as a child affected with
progeria Sam is 15 years old his parents
Scott Burns and Leslie Gordon both
physicians are here with us this morning
as well Sam please have a seat
so Sam why don’t you tell these folks
what it’s like being affected with this
condition called progeria
well progeria limits me in some ways I
cannot play sports or do physical
activities but I have been able to take
interest in things that progeria luckily
does not limit but when there is
something that I really do want to do
that progeria gets in the way of like
marching band or umpiring we always find
a way to do it and that just shows that
progeria isn’t in control of my life so
what would you like to say there
researchers here and in the auditorium
and others listening to this what would
you say to them both about research on
progeria and maybe about other
conditions as well well a research on
progeria has come so far in less than 15
years and that just shows the drive that
researchers can have to get this far and
it really means a lot to myself and
other kids with progeria and it shows
that if that drive exists anybody can
cure any disease and hopefully progeria
can be cured in the near future and so
we can eliminate those 4,000 diseases
that Francis was talking about excellent
so Sam took the day off from school
today to be here and he is he he is by
the way a straight A plus student in the
ninth grade in his school in Boston
please join me in thanking and welcome
Sammy well done
so I just want to say a couple more
things about that particular story and
then try to generalize how could we have
stories of success all over the place
for these diseases as Sam says these
4,000 that are waiting for answers you
might have noticed that the drug that is
now in clinical trial for progeria is
not a drug that was designed for that
it’s such a rare disease it would be
hard for a company to justify spending
hundreds of millions of dollars to
generate a drug this was a drug that was
developed for cancer turned out it
didn’t work very well for cancer but it
has exactly the right properties the
right shape to work for progeria and
that’s what’s happened wouldn’t it be
great if we could do that more
systematically could we in fact
encourage all the companies that are out
there that have drugs in their freezers
that are known to be safe in humans but
have never actually succeeded in terms
of being effective for the treatments
they were tried for now we’re learning
about all these new molecular pathways
some of those could be repositioned or
repurposed or whatever word you want to
use for new applications basically
teaching old drugs new tricks that could
be a phenomenal valuable activity we
have many discussions now between NIH
and companies about doing this that are
looking very promising and you can
expect quite a lot to come from this
there are quite a number of success
stories one can point to about how this
has led to major advances the first drug
for hiv/aids was not developed for
hiv/aids it was developed for cancer it
was AZT didn’t work very well for cancer
but became the first successful
antiretroviral and you can see from the
table there are others as well so how do
we actually make that a more
generalizable effort well we have to
come up with a partnership between
academia government the private sector
and patient organizations to make that
so at NIH we have started this new
National Center for advancing
translational sciences just started last
December and this is one of its goals
let me tell you another thing we could
do would it be nice to be able to test a
drug to see if it’s effective and safe
without having to put patients at risks
because that first time you’re never
quite sure how do we know for instance
whether drugs are safe before we give
them to people we test them on animals
and it’s not all that reliable
and it’s costly and it’s time-consuming
suppose we could do this instead on
human cells you probably know if you’ve
been paying attention to some of the
science literature that you can now take
a skin cell and encourage it to become a
liver cell or a heart cell or a kidney
cell or a brain cell for any of us so
what if you use those cells as your test
for whether a drug is going to work and
whether it’s going to be safe here you
see a picture of a lung-on-a-chip this
is something created by the vist
Institute in Boston and what they have
done here if we can run the little video
is to take cells from an individual turn
them into the kinds of cells that are
present in the lung and determine what
would happen if you added to this
various drug compounds to see if they
are toxic or safe you can see this chip
even breathes it has an air channel it
has a blood channel and it has cells in
between that allow you to see what
happens when you add a compound are
those cells happy or not you can do this
same kind of chip technology for kidneys
for hearts for muscles all the places
where you want to see whether a drug is
going to be a problem for liver and
ultimately because you can do this for
the individual we can even see this
moving to the point where the ability to
develop and test medicines will be you
on a chip what we’re trying to say here
is the individualizing of the process of
developing drugs and testing their
safety so let me sum up we are at a
remarkable moment here for me at NIH now
for almost 20 years there has never been
a time where there was more excitement
about the potential that lies in front
of us we have made all these discoveries
pouring out of laboratories across the
world what do we need to capitalize on
this first of all we need resources this
is research that’s high risk sometimes
high cost the payoff is enormous both in
terms of health and in terms of economic
growth we need to support that second we
need new kinds of partnerships between
academia and government and the private
sector and patient organizations just
like the one I’ve been describing here
in terms of the way which we could go
after repurposing new compounds and
third and maybe most important we need
talent we need the best and the
brightest from many different
disciplines to come and join this effort
all ages all different groups
because this is the time folks this is
the 21st century biology that you’ve
been waiting for and we have the chance
to take that and turn it into something
which will in fact a knockout disease
that’s my goal I hope that’s your goal I
think it’ll be the goal of the poets and
the Muppets and the surfers and the
bankers and all the other people who
join this stage and think about what
we’re trying to do here and why it
matters it matters for now it matters as
soon as possible if you don’t believe me
just ask Sam thank you all very much
you