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