- Good afternoon and welcome.
I'm Carol Christ.
I'm the Chancellor of Berkeley
and it's a delight to welcome you
to this event this afternoon.
You're here to hear a
conversation which has the title
The Future of Humans,
Gene Editing and the Unthinkable
Power to Control Evolution.
That title, to me, recalled
the 200th anniversary
of the publication of Mary
Shelley's Frankenstein in 1818.
Frankenstein is the prototypical
text of the human ability
to create new life, and it's
really a prescient text,
particularly at the moment
when scientists have the power
to manipulate the blueprint of life.
This is a bold topic, and
a perfect way to kick off
Berkeley's sesquicentennial,
which we're celebrating with
the official motto Fiat Lux,
or Let There Be Light.
This motto inscribed
in the university seal
and on the five-pointed
star that adorns Sather Gate
reminds us that it's our
duty to create new knowledge
and bring it to light,
to illuminate solutions for
the world's greatest problems,
and find solutions for
bettering the human condition.
As we celebrate 150 years
of light at Berkeley,
and we anticipate 150 years
of light in the future,
the discovery of CRISPR
by Jennifer Doudna,
and the global impact that this will have
comes immediately to mind.
Few breakthroughs in science have had
the kind of sweeping, immediate
impact that CRISPR has,
bringing monumental change to the way
scientists approach key questions of life,
and holding unlimited
promise for the future.
It's exhilarating to imagine
the transformations we'll see
as the result of this
technology in the coming years.
Our special guest Dr.
Mukherjee is an oncologist
at Columbia University
and Pulitzer Prize winner
for his book, The Emperor of All Maladies,
A Biography of Cancer.
His most recent book The
Gene and Intimate History
chronicles the history of the gene
and what becomes of humanity
when we can read and edit
our own genetic information.
A Rhodes scholar, he has earned degrees
from Stanford University,
the University of Oxford,
and Harvard Medical School.
Dr. Jennifer Doudna has been a member
of the Berkeley faculty since 2002,
and is the founding executive director
of the Innovative Genomics Institute,
a joint endeavor of UC Berkeley and UCSF,
and I'd like particularly to welcome
UCSF's Chancellor Sam
Hawgood to this program.
(audience applauds)
Since her days as a
graduate student and postdoc
at Harvard and the University of Colorado,
Jennifer has always been
interested in structural biology
and the biochemistry of RNA.
In 2012, she and her colleague
Emmanuelle Charpentier
discovered CRISPR, and
that's a game changer.
It holds potential to
cure genetic diseases,
overcome climate change, and
address global food security,
among many other
transformational applications.
Dr. Doudna's contributions,
her light, are significant
and worthy of celebration.
Please welcome Jennifer
Doudna and Dr. Mukherjee.
(audience applauds)
- Well, thank you, Chancellor Christ,
for that very warm introduction,
and thank you to all of
you for coming today.
We're really looking forward
to this conversation.
We will talk for about 45 minutes
and then we'd like to open
up the floor to questions
to answer thoughts and ideas
and give you a chance
to share those with us.
I'd like to start off by pointing out
that humanity has always had
a desire for improvement.
Cars, improved transportation.
Penicillin, improved health.
The internet improved the
spread of information,
or misinformation, in some cases.
Now it appears that we're
entering a new stage
of improvement, artificial intelligence,
to improve efficiency.
Self-driving cars to improve safety,
and the improvement of our own bodies.
So we have to truly ask
ourselves, what are we improving?
Do we need improving?
And even, what is improvement?
So gene editing technologies
and cancer therapies
are forcing us to look at these questions
and also to look at ourselves.
Cancer, for example, is a natural
and common cause of death.
Genetic diseases are too numerous to count
and a natural result of our being human.
A new wave of biomedical
advances are giving us
the ability to push back cancer
and erase genetic diseases,
but at what cost?
So I'd like to start this
conversation by asking you,
Dr. Mukherjee, are we transitioning
from natural to unnatural,
or is this just the next
step in human evolution?
- So, again, I think the
question of what natural
and unnatural is or are has
been really brought about
in the last decade or so
in a way with an urgency
that really didn't exist before.
Oscar Wilde famously said,
"Being natural is sometimes just a pose."
And the question is, how are we posing?
What pose are we on?
I do think that the
capacity to change something
as elemental as our own DNA,
even if it's in somatic cells,
certainly in stem cells and
certainly in embryonic cells,
really raises the question
about what we're doing
with our own evolution.
These are unprecedented technologies
because they allow us to hold
the horns of our own destiny
in some ways, even though
we understand destiny
is more than DNA,
but a powerful element
of destiny is in DNA.
You gave the example of
cancer and genetic diseases.
So really the question of what is natural
and what is unnatural,
the boundaries, I think,
have been redrawn or
are being redrawn today.
My own thoughts about this, really,
are the thoughts of a physician.
That's my brain.
I have a physician's brain.
And that is that as we do this,
as we enter this arena
of new technologies,
it seems to me that there are,
and I talk a little bit
about this in The Gene,
that there are a triangle of ideas,
which we should keep in focus.
The first one is when we intervene,
when we're intervening on human genetics,
is there extraordinary suffering involved?
You and I can then open
up a debate saying,
well, what is extraordinary suffering?
But at least there's a sense,
there's a hard line that we draw
and say that when we move forward
that that remains a
certain line in the sand,
that we invade on what is
natural versus unnatural
only when we think
that there's extraordinary
suffering involved.
In a second I'll tell
you that there are people
who don't buy this argument.
We'll talk about that in a second,
but that's one line of the triangle.
The second line of the triangle
is loosely I've called it,
in the book, I've called it penetrance.
The idea is, we can call it certainty,
that when we make genetic changes,
when we do tamper with evolution,
particularly with our own evolution,
that we have a strong degree of certainty
that there's a powerful relationship
between the gene and the phenotype,
or the ultimate manifestation
that's involved.
So things that we're uncertain about,
things that have effects
that we don't understand,
cascading effects, pleiotropic effects,
we probably should avoid since, obviously,
we don't want to intervene on things
that we cannot ultimately control.
And the third line of the triangle is,
I've called it, justifiable choice.
People have used different words for it,
and that is that when we intervene
between what is unnatural
and what is natural,
that the intervention
bears some justification,
that we can justify it,
and that it's not done by state mandate,
that individual choice is involved.
People are able to do it or
not able as they should choose.
Now, it doesn't take an
extraordinary complicated
bit of thinking to realize
that each of these is fuzzy territory.
Who defines extraordinary suffering?
Who mandates choice?
If our cultures push us towards
manipulating our children,
is that really a choice?
Even if it's a passive choice,
does it really become a choice?
- [Jennifer] And, by the
way, different cultures
might make different choices.
- For instance, exactly,
and you know better than anyone else,
the rules that apply for
interventions on embryos in China
are not the rules that
apply for intervention
in the United States and other cultures.
So I fully understand this
is complicated territory,
but as we move forward, if
we don't draw some stakes,
this is going to become, I think,
even more complicated than it is.
So it is absolutely true
that we're passing a boundary
between the natural and the unnatural.
Those terms were never easily defined,
never easily definable,
but the technologies are
forcing us to define them.
And my argument is that we should use
a kind of more sympathetic
way, humanistic way,
to try to breach those boundaries.
What do you think?
In fact, some of these
recommendations have been made.
You've been on panels that
made these recommendations
for intervention with human embryos.
What are your thoughts about
the breaching of the natural?
- Well, while you were
talking, I was thinking
that we had a meeting in
2015 in the Napa Valley
that was the first
meeting that was organized
by the Innovative Genomics
Institute and UCSF
to think about the ethical
and societal implications
of human genome editing.
And there was a fairly
small group of people.
We had two of the scientists
who'd been involved
in the 1970s discussions in Asilomar
about the ethics of molecular cloning,
Paul Berg and David Baltimore.
And even in that group of scientists,
there was a very active
discussion around the table,
heated at times.
People really disagreeing
and debating about,
in particular, human embryo editing,
so making changes that
would become inherited
in future generations,
and what would be the
implications of that.
And at one point, somebody
leaned across the table
and said, wait a minute.
There might come a moment
when we will consider it
unethical not to do that,
at least for certain kinds.
And it's like you're saying,
if there's severe suffering
due to genetic disease,
this might, in the future,
be something that we would
societally agree should proceed.
You know it's interesting for me,
because I have found that my own views
have been evolving over time.
- [Dr. Mukherjee] Yes,
you've written about this.
So tell us about the evolution.
- Yeah, I guess I started
off, when I first started
thinking about the
implications of gene editing
back in sort of the
early days of this work,
which was actually only
a few years ago now,
and started thinking about this.
I felt initially very
opposed to using gene editing
in embryos, not necessarily forever,
but I certainly felt
that the time wasn't now
to proceed to do that.
And why did I think that?
Well, it seemed to me,
it seemed unnatural.
It seemed something that
you were sort of messing
with something that maybe
you shouldn't mess with,
and as a scientist, I also
appreciate that in many cases,
a gene, and you know this
better than anyone probably,
but a gene that we think
has a certain function
might only play that role
in a particular context
of other genes.
So how can we ever really
be sure that something
we're altering might not
have unintended consequences?
And that would have consequences
in not only a person,
but all of their kids,
and their kids' kids,
and it seemed kind of a profound thing.
But what's happened over
the last few years for me,
and for those of you that don't know me,
so I'm a biochemist
and I've always done very
fundamental research.
So unlike you, Sid, I've
always just been working
on molecules rather
than patients or people.
But what's happened
over the last few years
is I've been coming into
increasing contact with people
that have genetic disease,
either themselves or in their families.
I recently got an email,
and this is very typical
for me these days,
but I got an email from
a woman who explained
that her beautiful, young
boy has a genetic disease
that had just been diagnosed,
and she sent me a picture
of this little baby
in his little carrier.
He's cute, and it just broke my heart.
It really broke my heart and
I guess I just found myself
recognizing that when
there is severe suffering
and we have an opportunity to change that,
it may be worth doing.
- Well, you know, one line
that philosophers have tried
to draw is between
emancipation and enhancement,
and they have tried to draw a strong line.
Of course, in real practice,
once you practice medicine,
those lines also become fuzzy.
What is emancipation for one person
can be enhancement for the other.
The extremes are quite obvious.
It's very easy to think about extremes.
Manipulating genes for cosmetic purposes
seems very obviously far outside the realm
of what we want to do,
but on the other hand,
there are certainly examples
where the conflicts are more real.
The question that occurs to me,
I'm gonna frame the question,
and then maybe subdivide it a little bit.
One question that occurred to me
while I was thinking about
this is we're always,
in medicine, straddling the line
between treating and curing.
But now we are beginning
to think about altering DNA
as a mechanism or a
means to treat and cure.
Is that reasonable?
And maybe you can speak
about it in three categories,
and divide it up as you wish,
but it seems to me that there
are three broad categories.
Number one is editing
genes of other organisms,
very widely speaking,
so all other organisms.
That's a little bit like saying humans
and all other organisms,
but really, imagine the
question of editing genes
in other organisms, in
crops and plants and pests.
The second is somatic gene editing,
so particularly things
like, I'm a transplanter,
so in stem cells, blood stem cells,
and other kinds of stem cells.
And the third, of course, is gene editing
in either sperm or eggs or embryos.
So tell us about what you
think the prospects are
in these three categories,
and is it reasonable?
What is reasonable and what's unreasonable
maybe in the three categories?
Or pick one of them which
is most provocative for you.
- Well, I think you're
touching on an important point,
and that is that gene
editing is used now widely
sort of across the biosphere,
I guess you could say.
It's really being used in plants, animals.
It's enhancing the pace of research.
It's opening up organisms
for study that in the past
really could not be investigated
at the genetic level.
So it's a very exciting
time, really, as a biologist,
I think, to be living in the midst
of this transformational
opportunity with new techologies.
And it's not just gene editing.
It's other things, too, of
course, that are converging
to give us ways that we
can manipulate organisms
that were unthinkable in the recent past.
So just having the ability
to sequence the entire genome
and all the DNA in the cell of an organism
and start understanding
what that code means,
how it dictates what an organism
becomes is really profound.
So just to quickly touch
on those three areas.
So if we think about using
gene editing in organisms
other than humans, clearly
this is going to have
a big impact on humanity, right?
Because it'll allow us to
change plants, for example,
to be more nutritious, or
to grow in environments
where they otherwise wouldn't thrive.
- [Dr. Mukherjee] Mosquitoes.
- Get rid of mosquitoes, maybe.
Maybe, or at least control
spread of disease by insects.
In terms of editing what you
referred to as somatic cells,
and just so that everyone's
on the same page with that,
that term just means
that we're editing cells
that are not germline cells,
meaning they're not cells that
are eggs or sperm or embryos.
So they don't cause heritable changes
in future generations of organisms,
but this could still
be incredibly impactful
for the clinical
application of gene editing,
and the type of research
that you do, for example,
being able to edit,
let's say, immune cells
so that they're more
effective at targeting cancer
would be amazing if we can do that.
Editing blood cells so
they no longer carry
the disease-causing gene
for sickle cell anemia
would be incredible.
And there's many, many
other examples like that.
Then the third category is the one
that is more kind of ethically
fraught, or could be,
which is, should it be okay or is it okay
to make changes in the germline of humans.
Believe me, scientists
are already doing this
in the germlines of
other kinds of organisms
quite routinely, but in humans, not yet.
And should we go there?
And I personally think
that it's going to happen
and it's partly gonna
happen because of the fact
that different cultures view
this question differently,
and I think we're seeing
already in the scientific world
that the pace of research, at
least, on human embryo editing
is proceeding differently
in different countries.
- So, just a quick
follow-up on that question,
and then we can move on.
How long 'til the first transgenic human?
- Um, oh dear, I'm on the spot here.
(audience laughs)
I don't know, is the short answer.
I think that, again, so
that everyone out there
sort of understands what's happening.
I mean, we saw, just
in the last six months,
there have been two very
prominent publications
in scientific journals from
highly respected research labs,
one here in the United States,
and one in the United
Kingdom, who both showed
that you could use gene
editing in viable human embryos
to change, to alter the genome,
to make a very precise change
to a particular gene in these embryos.
- [Dr. Mukherjee] There's
been some question about--
- There's been questions about the details
of how that's working,
but I think the overarching
thing that I take from that
is that this research is proceeding,
and I think the pace will accelerate.
I recently heard from a colleague in China
who is coming to visit me
here at Berkeley next week
who wants to give me an
update on his own research
in human embryos.
So it's moving forward.
I can't tell you when I
think it'll be actually used
to create a CRISPR baby, for example,
but I think we're seeing
steady progression
in that direction.
- I mean, just to give you one example,
I work with blood stem
cells and immune cells.
That's mostly why I'm a
biologist, leukemia doctor.
As of last week, we were just
talking about this earlier on,
as of last week, in cord blood stem cells,
we are getting gene editing successfully
in 90% of the stem cells.
In fact, we've gotten to a
place where we're wondering
if we should even sort these cells
because the efficiency of sorting
is getting to the efficiency of editing.
So basically I suspect
that the blood system
is open for business.
The entire blood system
is open for business.
There's many, many questions,
off target effects,
whether we will get weird
leukemias that arise
because we've made an
edit in the wrong place,
but essentially speaking, it's staggering.
We couldn't do this six months ago.
- So this is a very important point.
In the field of this technology
and all the things that
are being done with it
are moving forward incredibly quickly.
And one of the things
that's been on my mind
is how do we explain
to people that are not
down in the weeds doing the
work, working in the clinic
or working in the laboratory?
How do we explain what's happening?
Because I think we appreciate
that this is ultimately
going to affect everyone's life,
and I think that one of the ways
that people learn about science,
they learn about technology,
is actually through the media,
through Hollywood,
through books, of course,
and through fiction and nonfiction,
but they start to
understand what's happening.
We're seeing this, of course,
with artificial intelligence
has been all over the media lately,
and self-driving cars and things,
and a little bit genome
editing is creeping in there.
So I wanted to ask you what you think
Hollywood has done well and
what have they done poorly?
And how do we work with people
that like to tell stories
and they do that for a
business and professionally,
and work with them to get science right?
- Well, it's always a struggle.
One of the strangest
experiences of my life
was being a small consultant on Logan.
(audience laughs)
It's true.
If you were to sit
through the final credits,
I have a small, and
that's because, I mean,
I think I'm speaking correctly.
I barely enter particularly
the Hollywood world.
But I was approached by a
friend of a friend of a friend
who showed me the script,
and I said, well, you know the script
is really fundamentally
about a dystopic vision
of what happens when human
beings start reaching
for certain kinds of perfection.
It pushes towards the enhancement debate
away from the emancipation debate.
And my only thought about it
was I thought it's not dystopic enough.
(Jennifer laughs)
There's a moment in that film,
which actually I watched
a very early version of,
when you suddenly realize,
there's a moment in which the characters
are walking through a
corn field or something,
and you suddenly realize that
the entirety of the world
has now been transformed for human benefit
because the corn is
growing 10 times as high.
I think that was my input in the film.
I said make it more dystopic.
But just to remind ourselves
that I think the media has
a big responsibility here.
I think, again, it would
be very helpful for us
from the media to get a
road map of what the pulse
of public thinking about this is.
Because the media reflects
back to a large extent
what a much larger public
view of all of this is.
That would be what's helpful.
Not to set guidelines,
not to tell us about the science often,
but to tell us,
and that's what I think is
important about the films.
The film may get the science wrong.
They may get it too far
off, et cetera, et cetera,
but what they often get
right is they get the pulse
of what people's fears are.
What are they afraid of the most?
What are the concerns?
- [Jennifer] Or what
are they excited about?
- What are they excited about?
A film like, I'm just thinking
off the top of my head,
a film like Lorenzo's
Oil is a great example.
We could disagree about the science.
We know that it's very complicated.
People had disagreements, agreements,
but what it got right very
much was the obsessive hunting
of a parent for a cure for their child.
That's what it gets very right.
And as long as the pulse
is right, it reminds us,
it keeps us, I think, as
physicians, as scientists,
honest about what we're writing about.
What are the concerns?
Sure, we're talking about
powerful technologies.
Who's gonna draw the limits?
How are we going to move forward?
And I think that's what ultimately helps.
In some ways, Hollywood gets it right
when its moral compass is right,
when it sets our moral compass right.
Hollywood gets it wrong
when it tries to tell us
about science, I suppose, in a way
that doesn't make any realistic sense.
- So for me, I thought
the movie The Martian
was a great film that
really kind of captured
the excitement of an adventure
and the challenges that
one might imagine happening
if you tried to actually survive on Mars.
And it's sort of just beyond
where we think we are right now
in terms of technologies,
but I noticed that it captured
a lot of people's attention
and imagination.
I have a teenage son
and just hearing his chatting
about this with his friends.
You could just kind of sense this buzz.
So I think films like that are great
because they actually make
people think about science.
They think about the opportunities.
If we develop technologies,
that might allow us
to explore our solar system
in ways that we haven't been able to.
- [Dr. Mukherjee] Well,
sometime in the next few years,
there's gonna be a fictionalized version
of a Jennifer Doudna movie.
(audience laughs)
- Oh dear.
Horrifying thought.
- What would you like to
ensure is in that film?
- Is in or is not in? (laughs)
- Tell us both, tell us both.
Make it exciting.
- Again, I guess, to me, I
like it when films capture
the passion that somebody
has for work they're doing.
The struggles.
Students now will often ask me,
I feel almost a little bit embarrassed
because I think they think
that I've reached some pedestal
or something and I don't think
of myself that way at all.
I think of myself growing up
in this little rural town in Hawaii
and struggling through
general chemistry in college
and trying to figure out,
can I really be a scientist?
I think a movie to be true,
if it wants to be true,
and maybe it doesn't,
but if it really wanted
to capture anything
that's true about me, it would
have to show those struggles.
And it would have to show, again,
it's back to the human spirit.
All of us, I think, we have
passions for certain things
and that's one of the
things you learn in college
is you kind of learn about yourself
and what you find exciting.
For me, it was about
realizing I was just a person
that loved to think about molecules.
I loved to think about how life works
at the level of molecules.
But it hasn't been a straight path at all
and I would definitely want
a story to capture that.
- A lot has been written
about the initial series
of conversations that you had
with Emmanuelle at the start of this.
Actually, I've never read
about the kind of moment.
Was there a moment when
things crystallized for you?
- Well, I think there
have been a few of those.
When I think back on--
- Pick one.
- Pick one, okay.
(audience laughs)
Well, probably I should
pick the first one, then,
which is really when I met her
and we met at a meeting in 2011.
It was a meeting I almost didn't go to
because it was a meeting
for microbiologists,
which is certainly not me,
and I was busy and I was
teaching here at Berkeley
and I was juggling all the
usual things that we juggle.
I almost canceled it,
but then I decided to go,
and it's good that I did
because that's where I met
Emmanuelle Charpentier, and
she is a microbiologist,
so she had a legitimate
reason to be there.
When we met at this meeting, we met there
because we were both
working on what at the time
was a very obscure area of biology,
namely understanding how
bacteria fight viral infection
using a system called CRISPR.
It's an adaptive immune
system in bacteria.
So we were both giving
talks at this little session
at this meeting and afterwards
we went out to lunch,
and we started chatting and
we started walking around
the old cobblestone streets
of old San Juan, Puerto Rico,
and in that conversation, we talked about
starting a collaboration to
work together to figure out
the function of one
protein, just one protein,
that's part of this immune
system, a protein called Cas9.
It was a project that really
brought together expertise
from her lab as a microbiologist
and my lab as a biochemist,
and I do remember feeling
a real sense of the hairs
on my neck standing up
because I could sense
that there was something very
exciting about this project.
In some ways, the rest of
it kind of flows from that.
- So I can tell you my
story about that story
is that I heard about, from
all people in the world,
I heard about your early
results from Paul Berg.
I went to Stanford for another visit.
I have collaborators there.
I trained with Paul, and
Paul, as you very much know,
was among the many people
who discovered how to clone,
make recombinant DNA,
stitch two pieces of DNA
from two foreign organisms together,
and was instrumental in
the Asilomar meeting,
which was an important
milestone in all of this.
Once in a while, since
becoming a physician
and a scientist myself,
I'd go back to Stanford,
and I would always have lunch with Paul.
And these were very precious to me.
He's now 90 years old.
This was about when he
was 87 or something,
and he told me, you know,
I just heard a seminar
from someone and she talked
about an enzyme that allows you
to modify DNA in a site-specific manner.
And I thought, my God, the
old man has finally lost it.
(audience laughs)
I said, wow.
Because it was a little unfathomable.
People had been thinking
about this for a long time
and it was unfathomable
and, of course, the fact
that it was borrowed back
from (mumbles).
Just to move the conversation along,
flipping over the question of Hollywood
is a very pertinent
political question today,
which is, we are living in times
where the amount of distrust
for science is phenomenal
and I have to tell people constantly
that science is not fake news,
that there's a strong line
between one and the other.
Evolution is not fake news.
Bacterial evolution is not fake news.
So what do we do about this moment?
Do we have a responsibility?
We have really an unprecedented
moment in human history,
in American history, a country
that grew to some extent
politically out of
scientists and engineers.
I'm an immigrant, so the
history of this country
is a country that grew out of
the aspirations of humanists,
scientists, and engineers.
What do we do about this today?
What are you doing, Jennifer?
How does the world look to you?
- I'm very concerned about this.
I think it's a big challenge.
I think we have to start
by encouraging scientists
everywhere to get out of the lab
at some level and engage in conversation.
We have to talk about science.
We need to bring science
back into the discussions
that we have at cocktail
parties and things like that.
I think that books like
your books are doing a lot.
I think you're very
good at telling stories
that are very human and that
people can identify with,
so they don't necessarily think about you,
I mean, hopefully they think
about you as a scientist,
but they read the book because
it's really interesting.
It's really engaging, right?
It's not a textbook.
It's something that is very human.
I think the more that we can do that
and use language to
describe scientific ideas
that isn't filled with acronyms
and doesn't sound like a foreign language,
but we try to really just explain ideas.
Because I think, in the
end, a lot of the ideas
that we're having and thinking about
are not really complicated.
They're not.
It's just maybe the details are,
but I think the concepts
and ideas are not,
and this is something that
we just have to work at more
than I think we have
certainly in my lifetime
as a professional scientist.
How would you answer that?
- I can't agree more.
I think what I worry most about
is that there's a dispiriting
quality for young students,
for my students.
There's a dispiriting
quality in all of this,
and the dispiriting
quality lasts generations.
It carries through.
And I think this is an especial time.
I'm not gonna say it's not
go hug a scientist day,
but I think there's an especial time
when we need to remind
ourselves that the contributions
of science to this debate.
I mean, for instance,
look at climate change.
Before we have arguments and
conversations, we need data.
Data comes from laboratories,
from scientists who've
spent time gathering it.
We need to respect that idea
that we can't enter these
debates without data.
So just be careful, be
cognizant of the fact
that the scientists in
your life around you
are dispirited and try to encourage them.
It might be philanthrophically,
it might not be.
It might be personally,
but it's a tough time
for the graduate students
and the postdocs in my lab.
I don't know if you're
feeling that as well.
- So has your work and
especially maybe your writing,
has that led you to have
conversations and interactions
with new groups of people
that have sort of taken you
in new directions?
- Well, certainly politically, yes.
As you know, my first book
on the the history of cancer
was well read,
but then Ken Burns made
a documentary out of it.
The Gene is also going to be made
into a documentary by Ken Burns.
You should probably not tweet that
until it's formally announced.
(audience laughs)
- [Jennifer] No tweeting.
- It'll be announced in a week or two.
But we're in the middle of filming.
In fact, we filmed you, Jennifer.
And so I think that the transition
into serious documentary,
these are three hours, or
in the case of Emperor,
six hour documentaries,
allowed us to reach a group of people.
I think one of the most
interesting conversations
I've had recently is
with people who work on
education for children.
How do you take textbooks,
which are becoming more and
more outdated in some ways,
how do you convert that
into education for children?
How do you make it possible to put that
on the web to some extent,
but supplement that with
books that are more readable?
And that's an issue that
I'm very interested in.
How do you make a kind of
simultaneous storytelling
as well as didactic education
for AP, for instance,
which is much more accessible,
and doesn't remain boring or textbook?
- I think kids are actually
a great way in, too.
I had this great experience
a couple of years ago.
My son was in seventh grade at the time
and he was just taking a class.
They were teaching the kids about DNA
and so the teacher
asked me if I would come
and talk to the kids a
little bit about my work.
So I went to the school
and we did it after school,
so it was just voluntary.
We just asked the kids
who would like to do it
and my first shock was
I walked into this room
thinking there might be two, three kids.
There were 20 kids there,
and 15 of them were girls.
It was cool, yeah.
The other thing was, so I
thought, how am I gonna get
these 12 year olds
interested in what I do?
So I thought, well, I'll
take this 3D printed model
that I have of the Cas9 protein.
It was actually made by Jacob Corn,
who's here in the audience,
here at the Innovative Genomics Institute.
It's printed on a 3D printer,
but it's based on an actual
crystallographic structure
of the Cas9 protein, which is the scissors
that cuts the DNA and the
RNA molecule that programs it
to find and cut a
particular sequence of DNA.
That's what makes it a powerful tool,
and then the DNA itself getting cut.
So I took this model.
It's about this big.
It's about the size of a football or so.
I took it in.
The model was designed
by Jacob very nicely
so that it can be pulled apart.
You can actually pull the DNA out.
- [Dr. Mukherjee] You
should've brought it.
- You can see where the DNA got cut.
I should have brought
it, would've been fun.
But I took it to the kids
and I thought, well, I won't
actually take it apart.
I won't show them actually
how the DNA gets cut
'cause that might just be
too complicated for the kids.
So I had this model, but
it's brightly colored
and it looks kinda cool.
So the kids said, well,
can you pass it around?
So I started passing this thing around
and I was describing it to them.
Within five seconds, of
course, they had pulled,
they're like, oh, cool, the DNA comes out.
Hey, we can pop this piece off.
You know, they were dissembling it
and they were looking at it
and they were figuring it out,
and they were asking tons of questions.
Actually, they asked a number
of really interesting ethical questions.
I think one of the kids
at that little meeting
asked me about the ethics, not
really using that language,
but asked me, what does this
mean for changing embryos,
humans, and doesn't that
mean that you could decide
to make somebody taller or smarter or wow?
Just kind of grappling.
You could see the thought process going.
So I really think that the more
that we can reach out to kids
because kids are natural scientists.
They love questions.
And the more that we can do
that and get them engaged,
they don't think about science as a thing.
It's something that's interesting
that's entered their world.
- [Dr. Mukherjee] Are we
getting ready for questions?
- We want to turn it over to
questions from the audience,
but before we do that, I just
want to cover one more thing
with you, Sid, and that
is, I would love to hear
the motivation that you had
for writing your first book.
Because I think, for me,
The Emperor of All Maladies,
your first book about cancer,
it really is a profound work.
It's very, in some ways, very depressing,
but it's also incredibly
interesting to look at the history
of how humans have grappled
with this really intractable disease.
I'd love to hear what
motivated you to do it,
what was most surprising
to you about that process,
and was it fun?
Was it hard?
Tell us about that.
- So I had never thought
I would write a book.
I was trained as a physician scientist,
very nose to the ground,
and The Emperor of All
Maladies really grew out
of a patient's question, and
the patient's question was,
she was in the middle of
chemotherapy for sarcoma,
and she said, why are we doing
this and where are we going?
And it seemed to me just astonishing
that here was this disease
that has occupied our culture.
Cancer has become more than a disease.
It is a metaphor.
It is an allegory.
People use it to describe states of mind.
Very few illnesses in
human history have ascended
to this kind of space in human culture.
And yet we had no real history,
we had no book about it in the same sense.
People had written about
cancer in a thousand ways.
There were a million textbooks on it.
So that was really the
beginning of that book.
I started as a fellow
and during the day, I
would be in the clinic
and in the evenings, I would write.
It was just a journal to start with
and it grew and grew and grew,
and at some point of time,
I decided that I would
show it to a publisher.
Someone said to me, you know
there are gonna be two readers
for that book, your mother and you?
(audience laughs)
600 pages on cancer.
When it was first delivered,
someone said it was
like a phone directory,
from in the days when there
used to be phone directories,
a phone directory from hell.
(audience laughs)
it had a black cover.
In the back, in white, it
had cancer written on it,
and it was 1,800 pages long.
It had cut down to 600 pages.
So that's how I started.
That was my first book.
- Fascinating, yeah. (laughs)
Sounds hard, working in
the clinic during the day
and writing at night.
Wow, I'm amazed that you could do that.
And your second book?
So, well received as well.
Many people have read The
Gene that I've run into
just sort of randomly.
But also you encountered some
criticisms about the book.
Tell us about that experience.
- So, again, it's the
experience of distilling
very complex science to simple.
You can't satisfy everyone.
The simplification is
absolutely necessary.
Again, it was delivered
at 1,800-odd pages.
It had to be cut down to 600
and I have to do most of the cutting.
So things get left on the floor.
Things have to be cut off
and left on the floor.
So you have to have a
radical simplification
in many places and scientists
don't like being simplified.
They don't like their
work being simplified,
but in order to communicate
with a much wider audience,
you have to take away terminology,
take away even people.
Too many names becomes word salad.
Readers get switched off.
If you use too much terminology,
people get switched off.
So that's one.
So there's the criticisms
of omission is one area.
One of the controversial
parts the book involved
questions like race and IQ.
I really thought that for
this book, it was odd.
This was long before these questions
had become very central.
So there's a chapter on
race and a chapter on IQ,
both of which were read by
people I respected in the field.
Actually, Marcus Feldman over at Stanford,
who you know very well,
was a very important person
who read the chapter on race.
The chapter on IQ was also
read by many, many people
in the psychiatric community.
I really felt that those
were important to put in.
In retrospect, I feel even more strongly
that they were important to put in,
but there are disagreements
about some of these fundamental questions.
So it's part of the territory.
- [Jennifer] Yeah, absolutely.
- So maybe I'll continue this,
since we're speaking
about books and words.
You know, I'm very sensitive
to the idea of words around,
words like war on
cancer, battle on cancer.
Some people, some patients don't like it.
One woman famously said to
me, you go fight the war.
This is not a word that I want to own.
Others want to own that word.
It somehow helps.
The idea of them fighting something
in their own bodies helps them.
What do you feel about
the word gene editing?
Tell us what the various words have been
and what did you coin yourself?
What do you say yourself
when you use these words?
Genetic surgery has been
used to describe this.
What's your sense of any of this?
- Yeah, I think we've seen, I've noticed
an interesting evolution in
language around gene editing.
So it started off as people
would pretty much universally
call it genome engineering, right?
Genome engineering.
Obviously CRISPR was not the
first way to modify genomes.
There were earlier
technologies for doing this,
and they really were
engineering in the sense
that you actually had to
engineer proteins individually
to make targeted changes to DNA in cells,
and that involved a lot of work
and a lot of engineering in the lab,
engineering of proteins.
When CRISPR came along,
initially the same
language was applied to it,
but what's happened, and
this wasn't me at all.
This just sort of happened
organically, I think,
in the field, is that people began
to adopt the language gene editing.
Why?
Well, I think it's because
it sort of reflects
the maybe simpler nature
of this technology
in the sense that it doesn't
require a lot of engineering
for this tool to be employed in--
- [Dr. Mukherjee] When did
you hear that phrase first,
Jennifer?
- Gene editing?
- Gene editing, yeah.
- Gene editing.
I think it started sometime
back around the time
that we had the first international
conference in Washington
at the end of 2015 on gene editing,
and I think we used that
language for that meeting.
Maybe at some level, that
started to permeate the language
that was used to describe
it in other contexts.
But I started to ask people,
people like George Church,
when do you use editing and
when do you use engineering?
And I think it was George that said,
well, I really think that the
new ways of modifying genes
are much more like
editing than engineering
because we don't have to
engineer anything to do this.
We can just use the tool.
- Right, and do you think, moving forward,
this term will stick?
Is it easy for you now to use this?
Do you find there's a facility with it?
- I think so.
I mean, I'm curious to know,
and I try to ask this question
of people that are not scientists,
ask them how they react to that.
What does that mean to you
when someone says gene editing?
Does that mean anything
or is it just opaque?
But I think it's fairly
descriptive of what it is
that we're really doing.
Because if you think about
it, it's really a tool,
really a technology that's
all about rewriting DNA.
We've been able to synthesize DNA.
So we can write it, we can erase it,
we can cut and paste it,
and now we can rewrite it.
So I think it really is sort of analogous
to having a text editor that you're using
on the genetic code.
- One of the astonishing things,
I don't know how many people have worked
with the CRISPR-Cas9 system.
One of the astonishing things
as a user in human biology
is how simple it is.
It is very, very simple,
and maybe that's part of the captured
in this idea of gene editing.
It seems to me, one thought I
had is that for a long time,
I struggled with it to figure
out how it would help us
therapeutically in cancer.
Of course, to elucidate targets in cancer,
to genetically manipulate cancer cells,
it's really, really simplified,
but could we use this
therapeutically in cancer?
And I struggled with that for awhile,
and, of course, the
answer has now come to us.
You can't necessarily
use it in cancer cells
because evolution is working against you.
You have to essentially get it, we think,
in 100% of the cancer cells.
Otherwise, the ones that have
not been edited will evolve
and take over.
Maybe you can do it over and over again,
but the fact that the immune system
has now become quite clearly
one of the mechanisms
of controlling cancer,
and immune cells, you
can manipulate and edit,
and thereby reintroduce them.
So it's really given us a powerful way
to think about cancer,
not from the standpoint of cancer itself,
but from the microenvironment
around cancer.
Couple of questions that arise.
One is it seems to me that
editing sperm and eggs,
or sperm and egg making
cells, is going to be easier
than doing it in the entire embryo.
What do you think are
the prospects of that
and is that something, do you
see yourself, your own lab,
ever moving in that direction?
Making edited human sperm and eggs?
- So I think you're absolutely right,
and my disclaimer is that
I'm not a human developmental
biologist by any stretch,
but I think that from what
I've come to understand
from talking to people that
are experts in this area,
I think that this is absolutely coming,
that it's going to be possible,
and it's gonna obviate the
question of editing human embryos
because you won't need to.
- Which is much harder.
- Right, you won't need to.
You'll edit the sperm and eggs.
And would I ever do this in my own lab?
No. (laughs)
Not for any reason other than
that's not the kind of
biologist that I am.
That's not the kind of
expertise that I have.
But I think that you're right
that in terms of thinking
about future clinical impacts,
this is an area of very active development
where there's likely to be real advances.
- One piece of conversation
we were having earlier,
which is an important thread to pick up,
is that it seems that a
lot of the conversations
have focused around gene editing,
but we're also seeing the
simultaneous development
of other technologies.
You mentioned one of them,
embryology, stem cell biology,
and the third one is artificial
intelligence, deep learning.
I have a couple of thoughts
about deep learning and genetics,
particularly from the
standpoint of cancer,
but I'd love to hear
your thoughts as well.
One thing that occurred to me
was deep learning is beginning
to elucidate things about our genome
that I did not think possible before.
I read this fascinating study
of early cardiovascular disease.
So if you take cardiovascular disease
and you ask the question,
how many patients with
early cardiovascular disease
can be explained by single gene mutations?
And this is how we grew up as biologists.
We thought about mutation in
a gene affecting a pathway,
thereby causing the change
that leads to a disease.
Very classical genetic model of thinking.
And cardiovascular disease,
familial hypercholesterolemia,
you get elevated cholesterol.
You have all sorts of problems.
This study looked at
if you take 100 people,
only two of them, two of
those 100, can be explained
by these sort of powerful
single gene mutations
that will increase risk.
The question is, what about the rest?
What about the other 98?
And for a long time, we
didn't really know how
to solve that problem.
My colleagues in complex
genomics tell me now
that deep learning is beginning to solve
these kinds of problems,
that, in fact, it turns out
that complex human phenotype
can often be explained
by what I would call not shove effects.
So those single genes were like shoves.
They would push you
strongly in one direction.
But by nudge effects.
Often hundreds or often even
thousands of gene variants
that nudge you towards,
you know, have small effect
in and of themselves,
but as a network, or maybe in the context,
move you even a little
bit, even slightly towards
your ultimately.
So the question really arises
is that if that's going
to be the case with most human diseases,
does gene editing help with nudge effects?
Can you imagine ways or would
it only help with shove genes?
Are we gonna reach some
kind of biological limit,
as it were, to the capacity
to manipulate human phenotype?
It's a complicated question.
So I don't know what your
thoughts about that are.
- Well, I have two thoughts about that.
I mean, one is that I think that CRISPR
and gene editing technologies
that are coming from that
are going to help with nudge effects
in the sense that they're
gonna help us uncover
all the genes that are in those networks,
and that's already happening.
So there's lots and
lots of laboratories now
that are using gene
editing, not in the clinic,
but they're using it to understand
the genetics of human disease.
And they're doing it both in
human cells and organoids,
which are cultured bits of organs
that you can grow in the lab,
as well as in animal models of disease.
So I think that's gonna
be a very powerful way.
And frankly, I totally agree
with what you're saying
about using artificial
intelligence or machine learning
to help us understand those networks
'cause they're often complicated
and you have to really
understand all the players
that might be contributing
to a particular trait,
for example.
But the other way that I
think that gene editing
will potentially have an impact
clinically in the future,
and we're not there today,
but I think the technology
is going in that direction,
is being able to edit or
modify multiple genes at once.
- [Dr. Mukherjee] What's up with that?
- Well, sometimes these genes are found
in very disparate parts
of the genetic material,
but sometimes they're
actually co-localizing
in three dimensional space,
and there's more and more
that's being learned about
how that works in cells.
So I'm thinking that in the
future it may be possible
to use gene editing to alter
multiple genes at once,
maybe to remove whole segments of a genome
that aren't necessary for certain kinds
of developmental pathways, for example,
in particular cell types.
I think the opportunities
for using it as a real tool
of understanding of the
genome are still really
very much out there to be captured.
- So let me turn the
question that you asked me
in the beginning of the
conversation back to you.
What does the phrase human
evolution mean to you in 2018?
- What does the phrase human
evolution mean to me in 2018?
- [Dr. Mukherjee] How
has that changed for you?
- Well, I think we're on
this incredible continuum.
It really is an exciting time.
I feel many days a sense of wonder.
I feel amazed that I'm alive at this time
when we're at this moment
when all these technologies
are coming together
and, for the first time,
we can do things.
Like we said, in Chancellor
Christ's introduction,
we really have now the
power to control evolution,
and it's not just in principle our own.
That's obviously still
on the leading edge,
but to control evolution
of other organisms
in our environment.
It's a really profound opportunity
and a profound responsibility.
So I hope that we can all work together
and work as you're doing to educate people
about the science behind this
so they can think about it
and really contemplate what this means.
- [Dr. Mukherjee] Is it possible to have
an international moratorium
until we decide this is conceivable?
- No. (laughs)
No, it's really not, because
as we discussed earlier,
I think culturally there
are just many differences
in the way people approach these things,
and how would you enforce such a thing?
But I think what one can
do is engage in discussions
that are international, invite
people to share their views,
try to understand where
they're coming from,
and I think that's what
universities should be doing.
We should be encouraging that
and be really leading that conversation.
Not dictating it, but just inviting it
and welcoming different points of view.
So I would like to now open
up the floor for questions,
'cause I know that some
of you may have questions,
and we'd really like to
hear what you're thinking
and try to answer them.
So we have runners with
microphones that are coming around
and if you raise your
hand, they will call on you
and we will bring a microphone to you.
And who's calling out the...
- [Woman] I'll start on this side.
- The lights are in our face
so excuse us if we turn to you late.
Yes?
- [Man] Hi, thanks, it was a great talk.
My question is sort of quick.
I'm just wondering what have been
the three most
influential-slash-favorite books
for both of you.
- Well, it's interesting that you ask
because we were just
saying, this week, I think,
is the 50th anniversary
of The Double Helix,
Jim Watson's famous and at
one point infamous book,
which actually was really
a trailblazer for me
as a young reader, showed
the human process of science,
warts and all, and I was
very influenced by it.
I was also very influenced
as a young reader by Orwell.
All of Orwell's books were
very influential to me,
in fact, have influenced my thinking.
And then I would say, I
discovered in writing The Gene,
I discovered someone I
had weirdly neglected,
and I wrote about him recently
in an essay for The
New Yorker, Chesterton.
Now, you could say, well, what
about Chesterton and gene?
In fact, Chesterton wrote
very deeply about eugenics.
He was one of the great
skeptics of eugenics.
I discovered his writing much later,
and realized that there's
something wonderful
about his very bracing
skepticism about eugenics.
So those would be three
books sort of picked out
of a basket of thousands.
How about you, Jennifer?
- Yeah, fascinating.
Well, I have to say that
The Double Helix also for me
was incredibly influential.
That book was probably
the first book that I read
back when I was in grade
school about science,
and it kind of blew my mind.
For those of you that have read it,
it's really a very personal
history of the work
that Watson and Crick
and their colleagues did
to discover the structure of DNA.
It was really very eye-opening for me,
and really made me think
about becoming a scientist
for the first time.
And then the other two might surprise you.
Maybe not.
One is I would have to say
The John McPhee Reader.
I don't know if anybody
here knows John McPhee,
but he's a fabulous writer
and he writes about all sorts of topics,
and what he does is he
basically travels around
and talks to interesting people.
A lot of them are scientists,
but some of them aren't,
and he writes about it.
I found his writing to
be incredibly captivating
and interesting, again,
in my formative years.
And then more recently, I read a biography
of Dorothy Hodgkin that
was also just fantastic.
Learning about her life
and she had multiple kids
and she was working at a time
when it was very difficult for women
in science in particular,
and she prevailed, and
she won the Nobel Prize.
She did really just incredible,
groundbreaking work.
So that was also incredibly
inspiring for me.
- There's a little note in The Gene.
I actually met Dorothy Hodgkin years ago.
There's a little note in The Gene,
where when she won the Nobel Prize,
the subtitle in one of her photographs
was A Housewife From Sussex,
or wherever she lived.
(both laugh)
- [Jennifer] Oh, wonderful.
- [Woman] Hi, I think
I'm the next questioner.
- Where are you in space?
- Wave to us.
- Wave to us.
Oh, there you are.
- There you are, okay.
- [Woman] You talked earlier
about the cultural differences
or the difference in cultures
in terms of their approach
to the opportunity and
responsibility of gene editing.
Can you kind of talk a
little bit more about China
or other parts of the world
and what their approaches are?
And I think that's an
interesting piece for the public
to understand where things are going
in other parts of the world
and what your opinions
are about what's happening
in other parts of the world.
- You take that one first.
- Well, okay.
Again, this is really just my
personal observations, right?
But I think that what I've noticed is that
in certain parts of the world,
and I'm not putting any particular
country on the spot here,
but I think there are parts of the world
where there's an incredible
eagerness to be engaging
in the scientific process.
People that have felt
maybe not included in that
in the recent history
and wanna get into it,
and wanna be recognized for their work.
They wanna be prominent.
They wanna attract attention.
They want to make progress.
So I think there are
motivations that go beyond
the simple joy of discovery,
which I think all scientists share.
There also are people
that are thinking about
really putting their country
or their culture on the map
in terms of international recognition.
So I think that we're seeing
that there is some of that
that's driving the push
towards certain kind of edgier,
I would say, applications of
something like gene editing.
And that's where we
just need to be careful.
Again, what I've observed
is that there's a desire
on the part of scientists to be respected
by their colleagues, to be
accepted by their colleagues.
So I think there is a
willingness and an interest
in engaging in sort of an
international consensus
around what we all consider
to be appropriate use
of technologies.
That's just my observation
and I think that's what
we should be encouraging.
Because culturally people do approach
these things differently.
- And I would say even the
microcultures in science
are different.
We were talking about,
you know, once in a while,
I'll speak with someone
like George Church.
I actually had a public
conversation with George.
I talked about, George is a big enthusiast
of really opening this field up.
I think it's fair to say
he would be an enthusiast
of making directed manipulations
in human sperm and eggs.
And he thinks, that's his brain.
I think like a physician first.
My first thing that
comes out of my brain is,
"Are we ending suffering?"
"How can I first do no
harm?" is the first thing
that comes out of my brain.
People's brains are hooked up differently,
and I do think that
people's cultural brains
are hooked up differently.
Yes, there's a need for provocation.
Yes, there's a need to do as you work
to put people on the map,
but someone who's grown
up in, I grew up in India,
the cultural brain, you know,
what we think is permissible
and not permissible is different.
We have different
understanding, for instance,
of where life begins.
And that is important.
And it's so important that,
in fact, there will be places,
there are places that are drawing lines,
which then the lines don't
exist across the border.
Science will move in accordance to that.
If you wanna make genetic
changes in human sperm and eggs,
as a scientist, you would
relocate to a place,
if you badly wanted to do that,
you'd find a place to do it in the world.
So that's why I keep coming
back to this question.
We need to have some sense of boundary.
That's my physician brain speaking,
first do no harm brain speaking.
We have to have some boundaries.
I don't know how to reach them,
but I think they're important.
- [Man] Hi, question up here.
So one of the most surprising
things about genetics for me
was that effectively 97% of
DNA itself is noncoding, right?
And for awhile, there was
sort of the dead space
and you just assume that introns
were there for no reason,
and every time I look
at the literature still,
it's always kind of vague and confusing,
and it's like, well,
introns may do something,
they may have some role.
But I guess my question is,
what is the current attitude
towards introns in general,
with respect to DNA,
and do you think CRISPR
will ever become so advanced
such that these kinds of concerns
are going to become necessary in whether
we're gonna understand
something else about that?
I understand that's kind of theoretical.
(audience laughs)
- We're both pointing at each other.
- Well, let's explain
some terminology first,
just to widen out the question.
So one of the surprising things
that we learned as biologists,
in fact, this happens to be the 40th year
of the discovery of gene splicing.
And there was a big
symposium, I went to it.
So it turns out that, in
fact, a gene in the genome
is often broken up into parts,
and they're long parts that
are spliced out or removed
when that gene finally
becomes a mature RNA,
which then gives a protein.
So introns are those long
parts that are removed.
Exons are the parts that
ultimately make their way
into becoming protein,
and the question has to do with,
well, what about all those
introns and also the other space,
the intergenic spaces,
which for a long time
were called junk DNA?
That's a terms that we
inherited from the 19...
The history's interesting of that term.
We inherited that term
for really no good reason.
We inherited that term
from the 1960s and 1970s
when our understanding of the genome
was much, much more limited.
My one thought about this is for cancer,
it's turning out that those introns
and that the intergenic
spaces are turning out
to be extraordinarily important.
Not all of it, but much of it.
Jennifer, you refer to some of this.
It's not only important
in terms of regulating gene function.
It is important in terms of
the way DNA folds in space
and that also regulates gene function.
Some parts of it will turn
out to be unimportant.
There are lots of viruses
that sank their way
into the genome, which have been silenced.
In fact, there are whole
systems to silence these viruses
that might pop their
heads up from the genome.
So it's an active space,
but all I can tell you is that in cancer,
these previously
nonfunctional elements of DNA
are turning out to becoming
extraordinarily important.
And, by the way, how are we finding out
that they're extraordinarily important?
By using CRISPR.
By chucking them out
and all of sudden seeing
that they, in fact,
influence gene function
in ways that we hadn't
thought about before.
In cancer, that's a huge area of research,
but I don't know what your thoughts are.
- [Jennifer] Yeah, I don't
have anything to add.
That's exactly right.
- [Man] Over here.
- Yeah, sorry.
- [Man] My question is
regarding the accessibility
of gene therapy and CRISPR systems.
I mean, currently a treatment
with antisense oligonucleotides
is $400,000 a year,
and do you ever see these technologies
helping the entire world,
or just more well-developed nations?
- Yeah, well, it's a great question.
It's a really important question,
and something that I am
thinking about a lot.
I think this is on a
lot of people's minds,
and whenever there's a new technology,
you ask, what is this doing
to really help people globally
versus creating even
more inequalities, right?
And I think we'd all like
to see it do the former
and not the latter.
But inevitably when you
have new technologies,
it's expensive to develop those
and if you want to motivate
companies especially
to do the work that's necessary
to create a therapeutic
and go through all the clinical
trials that are necessary,
there is a big investment involved,
and that does lead to high costs
of those kinds of treatments.
How do you deal with that?
So one of the things that
I'm involved in right now
is some very active,
very exciting discussions
with our clinical colleagues
at UC San Francisco.
So through the Innovative
Genomics Institute,
we've been working on something
called the Genome Surgery Center.
It's in its fledgling stages,
but the real idea behind
this is to address
exactly the issue that you're raising.
I think none of us want
to see these technologies
develop to help the .01%.
We really want to see them develop
to help a much larger swath of people.
And so how do you do that?
How do you get there and
deal with the realities
of the costs of development?
So there's some really creative ideas
that are coming out of this.
We have here, of course, at UC Berkeley,
we have a lot of people
that are thinking about this
from the standpoint of
economics, sociology, history,
philosophy that we're engaging with.
Also at Stanford University.
And so, we have this great
intellectual community here
in the Bay Area to really tackle this,
and I'd really like to see us
take that on very directly,
and find ways to develop, for example,
just to give you an example,
what if you could find a way
to treat a large swath of people
that have a particular genetic disease
using one configuration of
a gene editing technology
that wouldn't require
individual clinical trials
for each one?
This would really reduce costs.
So we're looking into ways
that we can streamline that,
and to do that, we really
need to bring together people
that are doing the technology development
with those that are clinicians.
They know their patients
and they know what the technology
needs to be able to do.
It's a great challenge and
we're, I think, on the cusp
of being able to tackle it.
- I mean, sickle cell
disease is going to be
one of the first examples of this.
How we tackle it is really
gonna be one of the models.
Because, as a hematologist,
I've taken care of hundreds of patients,
young men and women, often
African-American men and women
with sickle cell disease.
It's a devastating disease,
debilitating disease.
You know, pain crises, opioid addiction
that comes with dealing
with these pain crises.
So it's a tough disease.
It is a disease that I think
is going to be very amenable
to gene editing based
technologies and transplantation.
It is on the cusp of becoming
very amenable to all of these,
and the question is, how
are we gonna price that?
And will we create a
gene therapy overclass
and a gene therapy underclass?
So that's one area that I think
that at least people like me
are very actively watching.
Thalassemia is another area.
We're on the cusp of these,
and I think those will be
models of trying to figure out,
can we offer gene editing
to people who really need it
without excluding them with cost barriers?
You have the mic, yeah?
- [Man] I have a microphone,
so maybe I'm next.
- [Jennifer] Okay, go for it.
- [Man] That was a really
fascinating discussion just now
because from reading the book The Gene
and also just thinking about
what we're going to do.
The first thing that comes to mind,
this wasn't my initial thing
I was going to talk about,
but it's wonderful to solve diseases,
but is the first disease
we're going to solve
be a white disease?
And that's just an aside based on
what you were talking about here,
and what you presented
about, underprivileged
or where the money is,
et cetera, Dr. Doudna.
- The quick answer is I don't think so.
I think that the first disease
that we're gonna solve,
I hope, is a disease of true suffering,
which is most amenable
to these technologies,
don't you think, Jennifer?
- [Jennifer] I do.
- I think that that's the first disease.
- [Man] I hope so, and
won't it be fantastic
when we solve that first disease?
But then my question was,
or where I was fantasizing,
and let's fantasize for a minute.
Our first trip to Mars was
a little bit tough, okay?
There was a certain group
of people who went there.
A number of people died there.
This is the fantasy, right?
- I see.
(audience laughs)
- [Man] And didn't really come out the way
they wanted it to.
But we're going back to Mars.
Shouldn't we be pre-adapted?
We need to modify our corneas
so we're not blind when we get there
through extended space travel.
Maybe we need to modify our gut
so that we can eat this simple organism
that we can grow on Mars.
Perhaps we should also address
the issues about our bones
so we won't collapse
and break like pretzels
when we get on Mars.
- You should come to our
workshop on astrobiology.
- [Man] Pardon me?
- Come to our workshop on astrobiology.
We're gonna talk.
- [Man] But now we're
pre-adapting a group of people
that becomes almost like a
plaid of people, if you will,
that are different from everyone else
because they are going to Mars,
and that just opens up the
thought about other plaids
of people as well for different purposes,
and really puts you into a territory
that could be quite scary.
- So I can give you my two bits on this.
Lots of people disagree.
I don't want to go to Mars right now.
I'd rather focus on cancer.
(audience applauds)
To me, the question is,
yes, the fantasy's lovely.
Lots of people disagree with me.
I actually got into a strange
argument with Jeff Bezos
about going to the moon.
The moon is a far away place,
which is very toxic for human beings.
It's not a great place
to carry heavy things to
because it's very expensive.
It's not a great place to put anything in.
There's a reason we aren't going there.
It has no atmosphere.
So I'd rather focus on curing
cancer and other diseases,
but I understand it,
that there is a desire to
escape these earthly coils.
It doesn't fascinate me as a question.
I don't know.
Are you fascinated by the question?
- I'm fascinated by the question,
but I'm even more fascinated
by asking the audience
to ask us one more question
(audience laughs)
and then we're going to
bring this to a close.
So do we have one more burning question?
Yes?
- [Woman] Hi, thank you for
the great talk, first of all.
I can already foresee many
ways in which genetic editing
could be beneficial to curing diseases
and just ending suffering
as you were mentioning.
But what I was wondering
is from what I know
and what I learned, a lot of
mutations occur just naturally
within evolution.
So I was wondering how,
or what your thoughts were
on how genetic diversity
could be affected by editing
and changing our genome.
- Well, the short answer
is not much anytime soon.
Because what we're talking about
is making very targeted
changes to the DNA of cells
that would be, at least in the near term,
this is gonna be done in people
in cells where it's
not a heritable change.
So you're really making a
targeted change in a tissue
or an organ in a patient, or
in blood cells, for example,
for sickle cell disease
and that sort of thing.
If you think in the longer term,
I still think that there's always gonna be
a background number of
mutations that are occurring.
Every cell division leads to
some random changes to DNA
that happen due to
various natural processes.
And what we're talking about here
is really just making one individual
or maybe just a handful of
individual targeted changes.
So if you think about that
in the context of evolution,
they're sort of intermeshed,
and you're always going to
have this background set
of changes that are happening.
I think the potential
to control those changes
and introduce changes that are gonna have
a real impact on disease
is a powerful one.
But I think, as you get from
this conversation today,
this is not going to happen
in any kind of a large sense
in the human population anytime soon.
I don't know how you would address that.
- I would put a word of warning on that.
I think it's a very important question.
The question of
diminishing human diversity
and having respect for human variation
is an incredibly important point.
I just often like to give
you the following example.
Privatized eugenics in
the hands of the citizens
of some parts of Northern
India has already created
a disgenic state where
because of infant neglect
or because of selective abortion,
the gender ratio in these parts
and some parts of the world
has now moved to 800 women,
800 girls, to 1,000 boys.
It's a profoundly abnormal, unnatural,
nowhere in human history
have we had 800 girls to 1,000 boys.
And that's mainly, because
of a combination of reasons,
but mainly driven by the
idea that one genetic makeup
is inferior quote unquote
to the other genetic makeup.
There's no state mandate.
In fact, the state prevents
you from doing this,
but privatized eugenics
has already diminished
human diversity radically in some places.
So I have to say, we have to
be extraordinarily careful,
even in handing over
to private individuals,
private citizens, the capacity
to select their own genomes
or the genomes of their children.
This is such a primeval desire.
To have the best children
is a primeval human desire,
and it is so primeval that
left in the hands of people
without cultural guidance,
without broad dialogue,
without inclusivity, without equality,
there is a rapid chance of it
devolving into a diminishment
or a reduction of natural
human variation and diversity.
Thank you for saying that
(audience applauds)
because it's a very important point.
And we've seen it happen.
Shall we?
- I think we're at the
end of our discussion,
but we want to thank
all of you for coming.
Thank you to the chancellors
of UC Berkeley and UCSF.
- Thank you for hosting me.
- And our hosts and all
of you for attending,
and we hope that you'll
continue the conversation.
Thank you.
- Thank you.
(audience applauds)
(percussive music)
