(ambient chord)
- Welcome to ATVB PVD 2017
here in Minneapolis, Minnesota.
I'm Kiran Musunuru, I'm
an Associate Professor
of Cardiovascular Medicine and Genetics
at the Perelmen School of Medicine
at the University of Pennsylvania.
It was my privilege this morning,
to participate along
with these two gentlemen,
in a special plenary
session on genome editing,
and specifically the scientific, clinical
and ethical considerations
around genome editing
in the year 2017, as things stand now.
As I said, we all had
some fun this morning,
participating in this session,
we each gave our little talks,
and then followed it up with
a very interesting polling
of the audience to get their
opinions of some of the issues
surrounding genome editing.
The therapeutic implications
of genome editing,
and even the possibility, down the road,
of human germline gene editing.
So I'm going to turn it over
to each of these gentlemen
to describe their
interest in genome editing
and how it's impacting the
work that they're doing
in their laboratories.
- My name is Joe Miano,
I'm a professor at the Aab
Cardiovascular Research Institute
at the University of
Rochester in New York,
and our lab uses CRISPR-Cas9
for the development of mouse models
to help better understand
cardiovascular diseases,
and other diseases as well.
We specifically edit the germline of mice,
and then use these mice to
ask fundamental questions
about the control of genes,
what turns genes on or
what turns genes off,
where and when,
and also the functionality
of proteins that otherwise
would be intractable to study.
- My name's William Lagor,
and I'm an Assistant Professor
at Baylor College of
Medicine in Houston, Texas.
And my lab works a lot with
adeno-associated viral vectors,
or AAV, and we're using this
technology to try and deliver
the CRISPR-Cas9 machinery to mice,
particularly to the
liver and other tissues,
to better understand the basic
biology of lipid metabolism,
to manipulate gene
expression and figure out
the contribution of new
genes to atheroscelerosis
and cardiovascular risk.
We're also trying to adapt
the CRISPR-Cas9 system
to pre-clinical genome editing of certain
rare lipid disorders in
hope that this will actually
provide some long-term
correction for people that
don't have a lot of treatment options.
So my personal interest in
CRISPR-Cas9 genome editing
is actually quite broad.
So my laboratory uses it in
almost everything we do nowadays
that just gives you some
sense of how transformatvie
this technology has been.
It really only emerged in early 2013,
and already it dominates
what every single person
in my lab is doing now.
Certainly we're using
it to answer a lot of
scientific questions, my
personal interest is in
risk factors for cardiovascular disease
and metabolic disease,
so blood lipid traits,
diabetes and so forth.
So, as Joe explained,
using CRISPR-Cas9 to modify
the germline of mice, making
so called knock-in mice,
knock-out mice, to really
get the sense of how
different genes contribute
to cardiovascular
and metabolic diseases.
But like Bill, I'm also keenly interested
in potential therapeutic
applications of CRISPR-Cas9.
So this morning I spoke
to one such effort,
which is to target the
gene PCSK9, which I think
many of you listeners will
be very familiar with,
it's become a hot therapeutic target,
there are two antibody-based
drugs that are
on the market now,
and just last month there
was outcomes trial data
showing that one of these
medications does in fact
reduce the risk of
heart attack and stroke,
which is a very positive thing,
it's a very exciting new
therapeutic class of medications.
And so we're targeting this
gene, but in a different way.
And that is to make permanent
alterations of the gene
within the genome, in the liver,
with the hope of eventually
turning off this gene,
so instead of having to take a pill a day
for the rest of your life,
or having to receive
injections of anitbodies
to clean PCSK9 out of the blood,
taking those injections every few weeks
for the rest of your life,
our objective is to see
whether we can devise
a one-shot therapy, using genome editing,
target the PCSK9 gene or other such genes
in a permanent fashion
so that you only need
to receive the therapy once,
and then you'll have lifelong protection.
So not unlike a vaccination, if you will,
against cardiovascular disease.
So I spoke to some of
those issues this morning,
with respect to the progress
we've made on those projects.
The other issue that I raised toward
the end of my discussion
in order to launch to a
broader discussion of the
ethics and social considerations
around genome editing,
is the whole idea of
human germline genome editing,
which has gotten a lot of press,
a lot of covers of magazines,
a lot of headlines in newspapers.
The idea being that we know
from the work of Joe and others
that CRISPR-Cas9 works very
effectively in mouse embryos,
which is very useful as
a research tool because
it allows us to make mouse
models of disease very readily,
but it turns out the same
technology, CRISPR-Cas9,
works pretty efficiently in human embryos
in those few studies that
have been published to date.
And so this has opened the door,
as many of you will appreciate,
to the possibility that one
day, not too far in the future,
CRISPR-Cas9 could be used to either repair
disease-causing mutations
or introduce protective
or beneficial mutations
within human embryos,
and then actually have
children who are born
who carry those DNA variants,
those protective mutations,
or who are free of
disease-causing mutations
that their parents might have.
And this is obviously a very touchy issue,
it raises all sorts of issues
that go beyond the bounds
of what we normally think
about in scientific discourse.
Issues of ethics, issues of morality,
issues of practicality in
terms of access to therapy
in an equitable way among
the entire population,
and so forth.
It also has really long-term implications,
because if this does come to pass
and the ability to modify the human genome
is done on a widespread basis,
we're really talking about
implications for the long-term
health and well-being
of the human species.
So it's not a trivial topic.
We had a very interesting opportunity,
and I think my two colleagues
here can also speak to this,
simply asking questions,
opinions, of the audience
about what they think
about some of these issues.
And so I was actually quite surprised with
some of the answers that we got.
I don't know if either of
you want to comment on it.
- Yeah I thought it was a
very informative discussion
of the issues, and it was
great to see the polling
of the audience to see
exactly where they stand
on these issues.
I was really struck by
the overwhelming support
for somatic genome editing
for therapeutic purposes,
and was also kind of
surprised to see just how much
support within our audience was present
for even editing of the human germline
in the right situations,
where it could be done just
depending exactly on the methods
that would be used to achieve that
might be a consideration.
But there seemed to be
a considerable amount of
support for that,
and as Kiran mentioned,
I think there's a lot of
very important issues that this brings up.
One is a very fundamental
philosophical issue
as to whether we're
actually going to change
what it means to be a human
being and alter our own DNA
from the very beginning.
And while the tools are
pretty basic right now,
this won't be the case in the future
and so I think this has
really profound implications
for society, I think it's
something that the public
needs to be involved
in, in this discourse,
and as scientists I think we
have to really make it our goal
to clearly communicate
the issues and concerns
and implications of this
research to the public,
and involve them in the conversation
and also be respectful of their views
on this very exciting technology.
- Yeah, so I quite agree.
I thought this was perhaps
the most entertaining part
of this morning's session,
having the audience actively
participate in answering
some of the questions,
these penetrating questions
that we're confronted with.
And it's important that
we have these discussions,
the National Academy of Sciences,
Engineering and Medicine
really call for, as a
mandate, public discourse
surrounding the use of
CRISPR-Cas9 genome editing
in the context of somatic
therapies as well as
the more thorny issue of
germline genome editing.
And so having scientists
sort of lead the way
in this discussion will
be pivotal in educating
the public and having them
weigh in on these weighty issues
of fundamentally changing who we are and
who the next generation of people will be.
Are we in a position to
make decisions for people
who don't even exist yet?
These are deeply philosophical issues
that need to be discussed
in the public realm.
And we do need to respect
the public, as Bill has said,
the variance of responses
that we'll get from people
from different cultural
backgrounds and socio-economic
status and so forth.
And so by having this discussion today,
I think that the American
Heart Association
is really going to be a leading entity
in ensuring that the public is informed,
and that their responses
to this potential therapy
are heard and respected.
- Yeah, so I want to
follow up on that and say
I think this is very important discourse
that we were able to at
least start this morning
by engaging so many people
in this thought process.
And we actually had an
audience of hundreds of people,
because it was an opening plenary
session for the conference
and so 200 - 300 responses for
the questions that we asked
of the audience, and then
a large number of questions
that were asked of the
audience, in reverse, of us.
And so, I think we're all
committed to finding some format
in which we can make the
results of our polling
available to the AHA membership
and really the public
at large to really help to
kickstart these discussions
that need to happen.
And so we close by saying that
this was a very instructive experience,
the results were not
necessarily what I expected,
but that I think is why we
do these sorts of things,
or why we should do these sorts of things,
and I think conferences like ATVB PVD
are wonderful opportunities
to have many people
in the same room to be able to
hash out some of these issues.
This is not the sort of thing
that would be so easy to do
if you're trying to do this remotely,
if you didn't have a big
conference where people
were getting together and mixing together
and having these conversations,
it would be very hard to do
if you sent a poll out
to very many people,
as you can appreciate, the
response rates to those
tend to be very low and
a person sitting at home,
watching a pre-canned
lecture and then answering
some of these questions is
a very different experience,
I think, than having
everyone in a room together,
really being able to feed off each other
with respect to the questions
that are being asked
in both directions.
And perhaps I'll close by just addressing
a very interesting question that came up.
So we're all very excited
about CRISPR-Cas9 gene editing
because, not only does it
underlie a lot of what we do
in our laboratories, but
it really does potentially
feed in to the AHA mission,
which is to reduce the risk
of cardiovascular diseases
and stroke and keep
people healthy of those,
healthy and free of those
diseases in the long term.
And I think, both on the
scientific side as well as
potentially the therapeutic
side, CRISPR-Cas9 is
clearly going to have an
important role to play.
But one very interesting
question that was asked of us
by an audience member was:
well if you are able to
eliminate cardiovascular
disease, does that mean
we're all going to die of cancer instead?
And it's one of those fun things,
I don't want to trivialize it,
but it's one of those fun,
interesting theoretical exercises
to think that, if we truly
are successful in our mission,
the AHA mission, to which
we're all firmly committed,
the point of the matter is,
everyone's going to die of something,
and I closed the session
with my observation that
it's not necessarily the
worst thing in the world
to die of heart disease,
but you want to do it
when you're 100 years old,
you don't want to do it
when you're 50 or 60 years old.
So the point is, really,
not to necessarily entirely
eliminate heart disease,
but really to help people
live free of heart disease
and stroke for very long,
fulfilling lives.
And that's really what I think
CRISPR-Cas9 and other types
of genome editing are
going to allow us to do
going forward.
Thanks so much for listening.
(ambient chord)
