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