The promise of research with stem cells Susan Solomon

so embryonic stem cells are really

incredible cells they’re our body’s own

repair kits and they’re pluripotent

which means they can morph into all of

the cells in our bodies soon we actually

will be able to use stem cells to

replace cells that are damaged or

diseased but that’s not what I want to

talk to you about because right now

there are some really extraordinary

things that we are doing with stem cells

that are completely changing the way we

look and model disease our ability to

understand why we get sick and even

develop drugs I truly believe that stem

cell research is going to allow our

children to look at Alzheimer’s and

diabetes and other major diseases the

way we view polio today which is as a

preventable disease so here we have this

incredible field which has enormous hope

for humanity but much like IVF over 35

years ago until the birth of a healthy

baby Louise this field has been under

siege politically and financially

critical research is being challenged

instead of supported and we saw that it

was really essential to have private

safe haven laboratories where this work

could be advanced without interference

and so in 2005 we started the New York

stem cell foundation laboratory so that

we would have a small organization that

could do this work and and support it

what we saw very quickly is the world of

both medical research but also

developing drugs and treatments is

dominated by as you would expect large

organizations but in a new field

sometimes large organizations really

have trouble getting out of their own

way and sometimes they can’t ask the

right questions and there is an enormous

gap that’s just gotten larger between

academic research on the one hand

and pharmaceutical companies and

biotechs that are responsible for

delivering all of our drugs and many of

our treatments and so we knew that to

really accelerate cures and therapies we

were going to have to address this with

two things new technologies and also a

new research model because if you don’t

close that gap

you really are exactly where we are

today and that’s what I want to focus on

we spent the last couple of years

pondering this making a list of the

different things that we had to do and

so we developed a new technology its

software and hardware that actually can

generate thousands and thousands of

genetically diverse stem cell lines to

create a global array essentially

avatars of ourselves and we did this

because we think that it’s actually

going to allow us to realize the

potential the promise of all of the

sequencing of the human genome but it’s

going to allow us in doing that to

actually do clinical trials in a dish

with human cells not animal cells to

generate drugs and treatments that are

much more effective much safer much

faster and at a much lower cost so let

me put that in perspective for you and

give you some context this is an

extremely new field in 1998 human

embryonic stem cells were first

identified and just nine years later a

group of scientists in Japan were able

to take skin cells and reprogram them

with very powerful viruses to create a

kind of pluripotent stem cell called an

induced pluripotent stem cell or what we

refer to as an IPS cell this was really

an extraordinary advance because

although these cells are not human

embryonic stem cells which still remain

the gold standard they are terrific to

use for modeling disease and potentially

for drug discovery so a few months later

in 2008 one of our scientists built on

that research it took skin biopsies this

time from people who had a disease ALS

or as you call it in the UK motor neuron

disease he turned them into the IPS

cells that I’ve just told you about

and then he turned those IPS cells into

the motor neurons that actually were

dying in the disease so basically what

he did was to take a healthy cell and

turn it into a six cell and he

recapitulated the disease over and over

again in the dish and this was

extraordinary because it was the first

time that we had a model of a disease

from a living patient in living human

self and as he watched the disease

unfold he was able to discover that

actually the motor neurons were dying in

the disease in a different way than the

field had previously thought

there was another kind of cell that

actually was sending out a toxin and

contributing to the death of these motor

neurons and he simply couldn’t see it

until you have a human model so you

could really say that researchers trying

to understand the cause of disease

without being able to have human stem

cell models we’re much like

investigators trying to figure out what

had gone terribly wrong in a plane crash

without having a black box or a flight

recorder they could hypothesize about

what had gone wrong but they really had

no way of knowing what led to the

terrible events and stem cells really

have given us the black box for diseases

and it’s an unprecedented window it

really is extraordinary because you can

recapitulate many many diseases in a

dish you can see what begins to go wrong

in the cellular conversation well before

you would ever see symptoms appear in a

patient and this opens up the ability

which hopefully will will become

something that is routine in the near

term of using human cells to test for

drugs right now the way we test for

drugs is pretty problematic to bring a

successful drug to market it takes on

average 13 years that’s one drug with a

sunk cost of four billion dollars and

only 1% of the drugs that start down

that road or actually going to get there

you can’t imagine other businesses that

you would think of going into that have

these kind of

it’s a terrible business model but it is

really a worst social model because of

you know what’s involved and and the

cost to all of us so the way we develop

drugs now are by testing promising

compounds on we didn’t have disease

modeling with human cells so we’ve been

testing them on cells of mice or other

creatures or cells that that we engineer

but they don’t have the characteristics

of the diseases that were actually

trying to cure you know we’re not mice

and you can’t go into a living person

with an illness and just pull out a few

brain cells or cardiac cells and then

start fooling around in the lab to test

for you know promising drug but what you

can do with human stem cells now is

actually create avatars and you can

create the cells whether it’s the live

motor neurons or the beating cardiac

cells or liver cells or other kinds of

cells and you can test for drugs

promising compounds on the actual cells

that you’re trying to affect and this is

now and it’s absolutely extraordinary

and you’re going to know at the

beginning the very early stages of doing

your assay development and your testing

you’re not gonna have to wait 13 years

until you’ve brought a drug to market

only to find out that actually it

doesn’t work or even worse harms people

but it isn’t really enough just to look

at the cells from a few people or a

small group of people because we have to

step back we’ve got to look at the big

picture look around this room we are all

different and a disease that I might

have if I had Alzheimer’s disease or

Parkinson’s disease it probably would

affect me differently than if one of you

had that disease and if we both had

Parkinson’s disease and we took the same

medication but we had different genetic

makeup we probably would have a

different result and it could well be

that a drug that worked wonderfully for

me with

actually ineffective for you and

similarly it could be that a drug that

is harmful for you is safe for me and

you know this seems totally obvious but

unfortunately it is not the way that the

pharmaceutical industry has been

developing drugs because until now it

hasn’t had the tools and so we need to

move away from this one-size-fits-all

model the way we’ve been developing

drugs is essentially like going into a

shoe store no one asks you what size you

are or you know if you’re going dancing

or hiking they just say well you have

feet here are your shoes it doesn’t work

with shoes and our bodies are you know

many times more complicated than just

our feet so we really have to change

this

there was a very sad example of this in

the last decade there’s a wonderful drug

and a class of drugs actually but the

particular drug was Vioxx and for people

who were suffering from severe arthritis

pain the drug was an absolute lifesaver

but unfortunately for another subset of

those people they suffered pretty severe

heart side effects and for a subset of

those people the side effects were so

severe the cardiac side effects than

they were fatal but imagine a different

scenario where we could have had an

array of genetically diverse array of

cardiac cells and we could have actually

tested that drug Vioxx in petri dishes

and figured out well okay people with

this genetic type are going to have

cardiac side effects people with these

genetics subgroups or our genetic shoe

sizes about 25,000 of them are not going

to have any problems the people for whom

it was a lifesaver could have still

taken their medicine the people for whom

it was a disaster or fatal would never

have been given it and you can imagine a

very different outcome for the company

who had to withdraw the drug

so that is terrific and we thought all

right as we’re trying to solve this

problem clearly we have to think about

genetics we have to think about human

testing but there’s a fundamental

problem because right now stem cell

lines as extraordinary as they are and

lines are just groups of cells they’re

made by hand one at a time and it takes

a couple of months this is not scalable

and also when you do things by hand even

in the best laboratories you have

variations in techniques and you need to

know if you’re making a drug that the

aspirin you’re going to take out of the

bottle on Monday is the same as the

aspirin that’s going to come out of the

bottle on Wednesday so we looked at this

and we thought okay our T’s ‘‘‘l is

wonderful in you know your clothing and

your bread and crafts but artisanal

really isn’t going to work in stem cells

so we have to deal with this but even

with that there still was another big

hurdle and that actually brings us back

to the mapping of the human genome

because we are all different we know

from the sequencing of the human genome

that it’s shown us all of the AC GS and

T’s that make up our genetic code but

that code by itself or DNA is like

looking at the ones and zeros of the

computer code without having a computer

that can read it it’s like having an app

without having a smartphone we needed to

have a way of bringing the biology to

that incredible data and the way to do

that was to find a stand in a biological

stand-in

that could contain all of the genetic

information but have it be arrayed in

such a way as it could be read together

and actually create this incredible

avatar we need to have stem cells from

all the genetic subtypes that represent

who we are so this is what we’ve built

it’s an automated robotic technology

it has the capacity to produce thousands

and thousands of stem cell lines it’s

genetically arrayed it has massively

parallel processing capability and it’s

going to change the way drugs are

discovered we hope and I think

eventually what’s going to happen is

that we’re going to want to re-screen

drugs on arrays like this that already

exist all of the drugs that currently

exist and in the future you’re going to

be taking drugs and treatments that have

been tested for side-effects on all of

the relevant cells on brain cells and

heart cells and liver cells it really

has brought us to the threshold of

personalized medicine it’s here now and

in in our family my son has type 1

diabetes which is still an incurable

disease and I lost my parents to heart

disease and cancer but I think that my

story probably sounds familiar to you

because probably a version of it is your

story at some point in our lives all of

us or people we care about become

patients and that’s why I think that

stem-cell research is incredibly

important for all of us

you