Thank you everybody for attending this panel
discussion about the documentary Human Nature,
hosted by Cold Spring Harbor Laboratory I'm
Elliot Kirschner, an executive producer and
producer on the film. This film was produced
by the Wonder Collaborative, a new initiative
to innovate science films for the general
public. My own background is in news and documentaries,
including a longtime collaboration with Dan
Rather a news icon who also served as an executive
producer on Human Nature. In fact, this project
began many years ago with an interview between
Dan Rather and Jennifer Doudna, who is joining
us here today and likely needs no introduction,
but nevertheless, Jennifer, if you would please
introduce yourself,
Thank you, Elliot. It's a pleasure to be here.
My name is Jennifer Doudna and I'm a professor
in the San Francisco Bay area. I run labs
at UC Berkeley, and Gladstone Institutes.
Right. And also joining us Alta Charo
I'll just share I'm professor of law and bioethics
at the university of Wisconsin
And Zach Lippman,
Thanks Elliot, I’m a Professor of plant
biology at Cold Spring Harbor Laboratory.
Wonderful. Well, we're going to jump right
in, I mean, one of the things that just sort
of this film is about is the fact there's
a huge story in science. A story that when
we started this wasn't getting enough attention.
So this gets a lot more attention now, but
since that time there's also been a whole
other obvious story, a tragic story that really
deals with science, and COVID-19. I think
one of the things I get a lot of questions
on sort of like the dress to you, Jennifer
is sort of where, where does CRISPR and COVID-19
come together? In what ways? There's a technology
that's about viruses and this is a virus and
we hear it about testing. Maybe if you could
give us a sense of where that is now.
Sure. Well, first let's just define the technology
we're talking about. So CRISPR is an acronym
that represents a bacterial immune system.
It's a way that bacteria can avoid viral infection.
In fact, the biology is very interesting.
There actually is a pathway for microbes to
find and destroy viruses that are in the process
of infecting them, or could infect them and
then provide protection in the future from
those viruses. So it's actually a system that
is, you know, a natural antiviral in the time
of a pandemic. I think this then resonates
with all of us. It's great to be able to use
a system like this to help us fight the virus
or certainly at least to detect it. I think
that, and I know we're going to get into the
other things that the technology is being
used for, but I think one of the extraordinarily
interesting things about what's happening
in science right now is that there are many
research labs, both academic and companies
who are beginning to use CRISPR as a way of
detecting the coronavirus and back developing
tests that could provide very rapid diagnostics
that allow sensing the viral genetic material
in a way that is very reminiscent of powders
and bacteria.
I think one of the things that makes it such
a powerful…CRISPR such a powerful gene editing
tool is sort of the specificity that nature
through billions and billions of years of
evolution has derived. So how does, how does
that sort of basic science, how was that harnessed
towards sort of this testing that you talked
about? It might there also be, might it also
become a tool in, in terms of treatments as
well as diagnostics?
Yeah, well, for diagnostics it's actually
used in a way that's very similar to how it
operates in bacteria, namely, to find a particular
piece of genetic material from a virus. And
for those that are a little further down in
the weeds, you know, coronavirus is an RNA
virus, that's its genetic material. And there
are some types of CRISPR systems that are
definitely, you know, programmed naturally
to identify RNA sequences. And so we use it
in the same mode as a diagnostic to find coronavirus
RNA molecules, and this can be done and they're
not just in cells, but it can be done in saliva
or maybe swabs, the kind of samples that are
being taken for testing with other kinds of
tests. And then, in terms of using it as a
therapeutic, it's an appealing idea that I
think in fact in will be difficult because
it would require delivery of these CRISPR
molecules into patient cells.
And as you can imagine, when that patient
is very ill with coronavirus and has those
ample infections in their lungs, and it might
be valuable to get an antiviral system to
that point in the body. Unfortunately, it's
just very difficult to do that kind of delivery
right now and get it into every cell where
it would be needed. So I personally think
that at least in the near term, this system
is going to be great for diagnostics. And
then, you know, when we think down the road
and how does science get ready for future
pandemics, there's where I think, you know,
there could be additional technical advances
that allow CRISPR to be deployed in a therapeutic
fashion in the future.
Wonderful. I want to add as it goes through
this, we do have a Q and A function in the
bottom and please populate that with questions.
I mean, there's no shortage of things to talk
about. We really want to, I mean, CRISPR is
such a diverse and interesting topic that
we really want to make sure we're answering
what people out in the audience are interested
in. But I mean, one of the things that we
did in this film Human Nature, and you can
tell from the very title, is that, you know,
there's a lot of questions about what this
means for human evolution. And, we try to
frame this in a sense that, you know, CRISPR
could change our ability to edit our own genes
and what that means. You know, a lot of there's
a real question about what the time horizon
is for that where everything is much faster
is really in other uses.
So I would like to sort of ask Zach to jump
in on this, and also these are things that
we've talked a lot about, you know, CRISPR
is being used in agricultural already. It's
being used in other forms, besides sort of
the human, you know, brave new world, which
we'll also talk about here too, but, you know,
I just think that there's a sense here about
how readily available this technology is in
some ways where it's already being used is
maybe gets less attention than it really should
in the popular press. So maybe Zach, you could
talk a little bit about where you think this,
where CRISPR is being used already in your research.
Sure. So we, as well as many others in
plant biology are using CRISPR extensively
in the initial desire to use it was as a tool
to study gene function. So the ability to
identify any gene that you'd want to study
its function you'd want to what's called knock
it out. And that essentially created a mutation,
a targeted mutation, but it quickly became
apparent that there were application values
to using CRISPR and my lab as well as others,
including Cold Spring Harbor, Dave Jackson
who works on corn, have been using CRISPR
to modify traits that are tied to agricultural
productivity. And I would agree with you,
I think the pace of innovation in plant biology
for using CRISPR, both in fundamental biology,
as well as applied science is really moving
very quickly. And I often describe it as a
freight train that really can't be stopped.
And some people don't like hearing that
because those who are, anti-GMO are always
worried about the relationship of what CRISPR
is and its technological use and agriculture
compared to the genetic engineering
that was pioneered in the mid 1990s. But
it's here, it's here to stay and it's extremely
powerful. And we're using it to, for example,
one case where we're, I think we're making
a lot of headwind is showing how we can convert
very tall, unwieldy growing tomato plants
into plants that are highly compact and very
rapid cycling, and they can be grown in urban
agriculture settings. So that's just one example
among many where it's being deployed and in
agriculture.
And I'll tell you, you and I have talked about
this many times, and one of the things you've
told us about the film is, you know, you were
a big fan there, you feel there are many other
films also about CRISPR and things that tackled
many different applications on it. And I think,
you know, there is this question about GMO,
about regulation, about how this technology,
how fast it's coming, how do you sort of,
how do you explain to people? And they can
ask questions. You followed this for, you
know, long before CRISPR and sort of seeing
this sort of field develop really rapidly
in many different forms of our ability to
edit gene. How do you, how do you sort of
address the timeline question and the application
question, you know, how fast it's going to
happen, where is it happening? And should one be scared about that?
I don't think the technology alone can
explain what the timeline's going to be. It's
also about whether there's some crying, unmet
need out there, that's driving people to use
it. So for example, when Zach talks about
its use in agriculture, we can imagine lots
of places where there might be interest in
having crops edited to deal with the changing
climate or to reduce the number of acres that
have to be devoted to agricultural practices
that might deplete the soil or to make
foods more nutritious, or to make them grow
a little closer to an urban center with a
smaller carbon footprint. So first you have
to have a pull mechanism. You have to have
people that are out there waiting for something,
right. And the second thing you need to have
is some kind of industry that's going to be
able to funnel money at an industrial level
to take things from laboratory through that
kind of intermediate pilot stage and put it
into widespread practice.
And last it's going to be a regulatory thing.
One of the differences between the human applications
and the kind of ag applications Zach mentioned
has to do with the regulatory regime, which
for many, not all, but for many engineered
plants is a lot easier than the regime that's
applied to anything that's a human therapeutic
that will be directly transplanted into the
body in the form of edited cells. And so that
makes it possible to imagine a business plan
that will result in some return on investment
within one's imagined lifetime. But
when talking about editing animals for
fluid or editing for human therapeutics, we
might be looking at decade or multi-decade
long timelines, right? So all of those factors
determine where the technology will go first.
One of the things that we often talk about
in these kinds of forums, obviously it's application,
but you know, before there's application,
there's basic research and Jennifer, you know,
you obviously straddled that divide and, you
know, and you say in the film, you know, you've
got on this when, you know, sometimes wondered
whether you were on a dead end of a field.
And one of the things we really wanted to
do in this film was to show how the process
of exploration, searching for knowledge, for
knowledge sake can lead to advances that you
can never predict. How do you, how do you,
when people talk to you about all the different applications that we already have a question about where
we're going to draw the line, and I hope other
people ask questions to the Q and A section.
How do you try to weave in the story of the
basic research? Because, you know, we live
in a time when, when basic research the funding,
the support is under attack and you know,
then it's relevant. But yet this really is
a story that begins with some very unusual
pathway in serendipity of discovery. Is it
not?
That's one of the things I love about the
story Of CRISPR. I think it's a great example of how
fundamental research conducted for curiosity
driven science can go in unexpected directions
and that's, that's absolutely the case for
this technology. I was, while you were asking
the question, in my mind, I was flashing
back in my mind as a graduate student. I think
I was probably a second year graduate student.
And I was, you know, I had arrived in grad
school, just loved science and wanted to do
cool stuff. I didn't know exactly what, and
I was working in a lab that was studying evolution,
molecular evolution, and doing experiments
that were ultimately designed to figure out...trying to answer something about
the question. What's the origin of life? Sort
of a huge question. And I had a little bit about
crisis, you know, when I was sort of in the
middle of my graduate career, because I suddenly
kind of started thinking, why am I doing this?
I mean, it's fun stuff and I'm having fun,
but is that okay?
Like, is it okay to have fun in the lab? Or
should I actually be trying to cure cancer
or, you know, do something "useful". I went
my advisor and I said, you know, why do
you do what you do? I mean, you're obviously doing
brilliant work and everything, you're a tenured
professor at Harvard, very, very accomplished
as a scientist. And he looked at me and said,
Jennifer, it's fine to do work that
is just designed to answer fundamental questions
about our current moment, you know, about life.
I think that is a great reason to do research
and I've never forgotten that because it kind
of resonated with me, you know, and I sort
of felt like I finally got it,
but nonetheless like many scientists, and
I think as I went through my career, I was
always trying to kind of look for ways to
make some kind of connection to real world
problems. And ironically, CRISPR was kind
of my one little area of research that I carved
out thinking, well, this'll just be for pure fun. There's nothing useful here.
It's just, I'm going to have fun with this.
And carve out a little bit of money to work
on it. And that was the area that, in the end,
you know, probably in my career, will be the most
useful thing that I've done, I think it's
just a great, you know, great example of the
serendipity itself.
And in fact, how do you, I mean, you yourself
as a researcher, how do you walk that line?
I mean, how do you know, obviously the applications
for your research are very evident in terms
of real world the way that also talks about
needs are so evident, but yet, you know, there's,
there isn't a need also to just get some fundamental
understandings and, you know, how does one
balance the drive for sort of real world product
with just the search for knowledge
and how does one lead to the other end. And
then, and then also the follow on the back
of the loop, how does, how does her application,
how can that also then drive basic research,
especially in regards to CRISPR, you think?
Yeah, there's a lot to unpack there. In
my case, the primary interest is fundamental
biology, in fact evolution. So I'm most interested
in plants in general and how they make flowers,
where they make flowers when they make flowers.
And that of course is important in agriculture
because flowers drive fruit and seed production.
And this question of evolution is something
that's very fundamental. You know, there's
really no immediate practical value, but we
know in agriculture that evolution and evolutionary
change is what drives the crops that we eat.
Right? So the changes that were important
for corn to be corn or for tomato to be a
large fruit or because of evolutionary changes
that naturally occurred and then were selected
by humans thousands of years ago, all the
way up to the present day. So it's an inexorable
link between the two and the desire to study
those genes, what we call pathways and networks,
that control these traits that are important
in evolution, either for adaptation in the
wild or in the sense of first stages
of agricultural production of these crops,
you know, from their wild ancestors, these
are just connected, you know, inevitably.
And in terms of, you know, when things
lead to application, they inevitably feed
back to the fundamental because you're always
getting surprises. So, I mean, there are a
number of surprises that I won't go through
here, but we do some things in terms of application.
And I work primarily on tomato and we'll
make these genome edits of a certain gene
in one variety of tomato and then another
variety, and you think that the outcomes will
be the same, and they're different. So why
are they different? And there's differences
because there are other natural mutations
that exist between the two varieties that
you didn't see and didn't know about, but
the genome edit that we created revealed those.
And so that leads you down a whole different
path of discovery.
And when you talk about sort of this surprise
and the serendipity, and really a sense, that we really try to put in our film too, a
sense of humility and modesty among science,
about how, what, how much we really do know,
and, and sort of how hard it is to predict
where we're going to go. And especially around
questions of evolution, we really brought up
to an essential question that we try to address
in this film. And also I think this is, this
is the topic of our first, our first question
from the audience and others, please fill
out the Q and A form and add more, but, you know,
personally, I like what you said in the movie,
where do you think society should draw, and
will draw the line? In the future, do you
think people will be able to customize or
engineer that genetic trace mutations in their
own children? And I mean, ultimately, no matter
how we're talking about this technology, no
matter what the audience is, some version
of this question comes up. You've heard
it from many forums around the world. And
so how do you, how do you respond to that?
Keeping in mind, what we've just heard from
Jennifer and Zach about sort of the role of basic research,
the unknowns of how that, how that of applications
around a technology, as powerful as that?
Well, for me, I think it's important to think,
not only about the technology, but what we
know about human behavior. And so since about
the 1970s, we've seen the series of reproductive
technologies that have given people increasing
amounts of control over birth outcomes. We
had amniocentesis in the 1970s, and then we
had in vitro fertilization and artificial
insemination in the 1980s, where you could
pick your egg donor or pick your sperm donor.
By the 1990s, you could diagnose your embryos
and only use those that were free of some
particular trait or mutation that concerns you.
And at every stage, if you look at the literature,
you will see that there is a consistent concern
that this is going to become widespread, that
everyone will start doing this and that that's
going to fundamentally alter the evolutionary
direction of humankind. Couple of things first,
First, no, it hasn't been something that everybody
does.
And not only because it's not affordable and
not even only because there are always risks.
Although here, there are very substantial
unknowns about the risk factors that still
need to be explored, but simply because in
most cases, people don't want to go to that
kind of effort for return that is just not
that important. And second, they are more
concerned about having children that resemble
their partner than they are about having children
that are somehow optimized. We know this because people
have been offered free quote unquote superior sperm
Superior because of reported intelligence
as if that's inherited, superior because of
attractiveness by some measure. And what we
see is people don't take advantage of it in
large numbers. Where you do see uptake is
where you have devastating illnesses and where
people do still want to have a genetic connection
to their children,
but don't want to have the children suffer with those kinds of illnesses.
The second thing is that if you're talking about
evolution, you've got to remember just the
numbers game. In order to alter the direction
of human evolution, the number of people who
have to do this and do it in a particular...
in particular way is enormous. I mean,
unimaginably launched to make that kind of
have that kind of effect. And it also tends
to presuppose
That evolution you're supposed to go in one
direction or even that we're supposed to be
getting better and better. And neither of
those things are true. Evolution's a lot more
random. So I'm able to live with the technologies
without nearly the level of anxiety that some
other people have about the way they'll expands
into uses that we find regrettable.
There'll be pockets of it. There'll be some people who
use it for things that I personally find offensive,
but I don't see it changing the fabric of
society in a way that is really devastating
to our society.
We have a question Jennifer for you here,
but it touches across something that I think
was one of the inspirations and excitement
about us as filmmakers tackling the subject
is when we talk to the scientists, you early
on, and to some others, it was very clear
that, that there was not a divide where we're
going to have sort of, we could do a film
where the scientists were on one side in a
monolithic way of doing things and the ethicists
were on the other and we could pit everybody
against each other, rather than the scientists
themselves, as part of the human population,
not as special subspecies sort of were
grappling themselves, and you in particular
with the questions of the ethics around this,
and, you know, so here's a question. What
do you think of the role of ethics plays in
advancement of evolutionary biology specifically
related to CRISPR, and more specifically regarding
the future studies, which could involve CRISPR
to cure human genetic disorders and other
problems arising of the applications of CRISPR
and the ethical applicant implications on
a wider society? How do you, how do you
A, view the ethics, but I also would like
to sort of get a sense of how do you view
your responsibility in this community
and in this discussion, in discussing the
ethics and confronting that in your own
research? And then, and then the policy positions
that you choose to take or not take?
I think it's critical that scientists are
engaged in these discussions. And I think
it's absolutely critical also to build a global
community of discussions around these, these
topics. I think, you know, CRISPR is one
of multiple technologies that are coming along
that are going to impact our world profoundly
in the coming decades. So I think that, you
know, building a culture where scientists
and technologists who are developing these
things are, you know, are engaged deeply in
those discussions is very important. I was
educated at a time when, at least in my
experience, you know, students were mostly,
you know, kept in silos. You know, we
had, you know, we were, we were doing our
experimental work and there was some lip service
given to ethics in science. But my course
in that topic was primarily about, you know,
what is plagiarism and things like that, right.
There's nothing about is your work to impact other people in a
profound way that you need to be aware of
and thinking about and engaged in. And so
for me, you know, when, when CRISPR came along,
our early work in this field, you know,
once was, it became clear that this was going
to be a really transformational technology.
I had to, I had to sort of forge a path that
I, you know, didn't have any experience
on. And fortunately we have people like
Alta Charo who have been leaders in this area,
who are really thinking about the ethics of technologies
and especially in the arena of reproductive
technologies, but,  you know, and, and
Zach, I mean, in your, your field also, right?
I mean, really, you know, there's been a long
history of misinformation, frankly, I think
around the way that plant breeding is
done and what the outcomes of those experiments
are afterwards in, in heaters laboratories
are and what the impacts are.
So, you know, for me, I guess, I, I just,
you know, I've been really trying to, first
of all, learn about some of the ethical challenges
that scientists and all of us really have
faced in the past around technologies
and their applications, and then going forward,
looking for ways to build transparency into
our system, to look to, you know,
as much as possible kind of global scientific
consensus around responsible use of CRISPR
technology. There's another question that
you know, is really relating...
related to this in the sense that, you know, will
it be possible to have global regulations
around the use of CRISPR? I feel there won't
be, you know, I don't think so. I think maybe
the best we can hope for is, is to have a
community of scientists and, and prominent
people in the field who speak up and are in
alignment about this. But ultimately
I think that, you know, we won't be able to
really control, whole control these technologies
going forward. Does that mean we should just
ignore it and carry on in our labs and say,
well, that's somebody else's problem?
Absolutely not.
One question that we get a lot, and also I
want address to you here is sort of, you know,
this is science is a global enterprise,
we're seeing with the pandemic, how, how different
global responses are to, within different
countries and societies and how different
places approach science differently and control
limits differently. We're also at a period
of incredible social unrest and rising questions
about the totalitarianism and pacifism
and all of that carries know long histories
around obviously genetic manipulation and
judging people and classifying people around
genetics, sort of, it was a question here
about how do you think, how do you think this
will be, can and will be regulated, you
know, in terms of a global community. And,
you know, and it...might have what Jennifer
said, you know, about how hard it's going
to be to control and how, how do we, how do
you see that playing out? I mean, I think
this is a question you get a lot, we get a lot
So Jennifer is absolutely right when she says
that it's difficult or even almost impossible
to imagine a truly global governance system
that said, it is possible to try to build
frameworks that let each individual country
using its own cultural values, adopt a system
that's more responsible than simply having
no regulation or no law at all. And the world
health organization now has a committee that's
trying to do exactly that. Basically give
governments guidance. I'll talk now only about
human therapeutics. If you're going to approve
human therapeutics for somatic editing, do
you have an agency capable of doing the following
things? And you talk about the kind of evaluation
of preclinical evidence, the management of
clinical trials, the oversight and surveillance
needed to look for side effects. And if you
don't have that, then are you able to partner
with an entity that does? And are you, are
you prepared to think about the following
questions?
How are you going to distinguish between things
that are therapeutically important enough
to do, even when we're talking just somatic
versus those things that people might call
cosmetic or enhancing and are less compelling,
how are you going to manage cross border differences?
If a patient from another country comes to
your country because your country is more
liberal or vice versa, one of your people
goes to do something that would be illegal
at home, then they go abroad to do it. And
if your scientists want to travel across borders
to do research, that is, or is not legal,
how do anticipate these kinds of things, but
we can't expect every country to have exactly
the same rules and the same values. And that
goes doubly in when it comes to heritable
forms of editing in which we are going have
many countries that simply say it is criminal
act and already do, a lot of countries in
Europe already say that.
So it's going to take time to see how
the regulatory system develops layered on
that is exactly what Jennifer said, the real
need for the scientific community to be organized
well enough amongst themselves, to be able
to call out somebody's work if it seems problematic
and bring everybody's attention to it early
on, and to have a venue where they can debate
this and educate one another about their concerns.
And there is an international commission that's
going to be reporting out in September, that's
looking at only heritable forms of editing,
but it's also looking very specifically about
how the scientific community can self-organize.
So we're beginning to make progress, but it's
very incremental. And we haven't even touched
Zach. I'm sorry, on the complexities of genome
editing versus transgenics when it comes to
crop regulation, but I'll let you tackle.
I want to jump in there because I want to
turn this discussion a little on its head
from what we normally hear when we talk about,
and we have a question for example, about,
you know, the risks that we can and therefore
will identify a deleterious gene that can
be fixed with CRISPR, that turned out in the
future to be advantageous, and this specific
question here about the wholesale, which we
addressed, which obviously confer some protection
to malaria. And we've talked about
that in this film, you know, a wonderful example
of David Sanchez, and his very inspiring
story and sort of his own perspective on this
question. But I think that we've already established
that this, this stuff is coming much more
quickly in agriculture. We have a lot, we
have, we have examples of, of a GMO debate,
around agriculture and that in some ways,
you know, we've also heard how hard it is
to really change human populations at, at
at a scale where you're really effecting
evolutionary trends rather than just individual,
you know, sort of variation on a more micro
level.
But it seems to me that when we talk about
deleterious genes, when we talk about our
own humility, that really an agriculture,
I really want to sort of probe this question
in the agricultural implications. We have
another question about having cows making
better milk or something like that. You know,
what kind of, what kind of questions and humility
do you think we need to do around genome
editing in the field where you're studying
Zach, it is in some way, much more, you know,
maybe if you could get out more quickly or
it might not be noticed as much, or has a
much quicker turnaround time in terms of how
something can spread and that the level of
human genetics. So how do you sort of look
at these questions about, about sort of risk
and benefit and our level of knowledge?
Yeah, that's a, that's a good one. You
know, at one thing I'll start with is saying
that an agriculture mutations that are considered
deleterious in nature are often advantageous
in agriculture. So there are a number of cases
where there are what we call domestication
syndromes. And really what that is saying
is that there are substantial modifications
to traits that would not be adapted to the
wild, but for agriculture they're wonderful
high yield, compact plant, rapid flowering,
various other characteristics. And these are
mutations that are desirable and they are
selected for, they have been selected for,
and they continue to be selected for. And
we've learned over the last three, four decades,
many of these genes that are responsible for
these modifications, that would be deleterious
in the wild. What I think also is relevant
here is the fact that genes, and the traits
that they impact are not in this vacuum in
the sense that they're often affecting multiple
traits.
They act what we call genetics, pleiotropic
weeds. So they'll affect leaf development.
They'll affect the root architecture, they'll
affect their interaction with the daylight
of wherever they're being grown. And
oftentimes we have this assumption, and this
is where I think your question is relevant
for the unexpected. We have this assumption
that this particular change that we're going
to make by genome editing to one, two, 10 genes
will result in these predictable trait modifications.
But there's so much we don't know about genes
and their roles in various aspects of development
that we have to be again, humble and expect
that we're going to find things that are not
going to be that advantageous. But here is
where I say, this is not necessarily an issue
that should affect regulation nor should affect, humans concern about consuming genome
edited crops, because this is where breeders
and the savviness of breeders and the artistic
approach that breeders take to improving crops
comes in. They will select against things
that are undesirable. They will immediately
say this genome edit you made you think it
looks good for this trait, but now I have
a problem with that trait, it's gone. We don't
need it anymore. And so I think the breeding
side of things will never go away. The very
traditional breeding approach infused with
the genomics technology that we have in the
genome editing technology become a menagerie
of tools that basically will self reinforce.
And so the best modifications have negative consequences.
As a follow-up, do you find that what you see in the field
brings any sense of pause or perspective about
using this technology at this time?
Right.
Are there any lessons from what you're learning
there that can give us a sense of what some...
of what the some of the struggles might be, or
some of the hurdles might be in terms of,
I mean, obviously it matters a lot less if
one in 10 tomato plants dies because of the
off target effect or something like that,
as opposed to a human at that level, but you
know, one in a million would be
Considered unacceptable.
Well, so I'm just curious what, what you're
seeing, what do you see in the field literally
that might give relevance to this larger discussion in use in humans?
Yeah, so, so here's the joke. So we walked
down the rows and we're looking at our genome
edited plants and we see something we don't
like, we looked to the left, we looked to
the right and we go down and we rip it out
and we throw it to the side. So it's pretty
easy to get rid of these things. And, you
know, we don't feel ethically bad about this.
This is part of the wonderful thing about
being able to work on plants is there are ready
and amenable to these types of modifications.
I think it's more a question of still
we're in the infancy of just understanding
the traits that we want to modify. And what
I mean by that is that genome editing is often
being pitched as a way to have plants be adapted
for climate change. There is so much, we still
don't know about how plants themselves are
adapted and interacting with their environment
and the many genes that are involved in this
that we don't have a clear handle on the targets
that we want to go after.
So what we're doing are these baby steps and
they look impressive because visually they're
beautiful and they're impressive, and they
really can tell a story of what's possible,
but on the ground, it's a lot more complicated
than it seems. And I would say for Alta and
for question of humans and human evolution,
you know, changing traits that are polygenic,
in other words, involve multiple genes, we're
still way at the infancy of being
able to understand which genes we would be
able to modify. And so I would agree with
Alta that when it comes to disease and correcting
deleterious mutations, we're gonna make a
lot more headway there. But the likelihood
of us being in a position in my lifetime to
be able to edit genes that would modify these
quantitative traits that have multiple aspects
of control of various different
growth parameters. It seems very, very challenging.
We'll get there, but it's going to take a
long time.
And just add to that because Zach, when you
were talking about looking at plants and then
it's been edited and finding that an edit
in one tomato background gives very different
results than in another tomato. They're both tomatoes but genetically they're
just different, you know,
and I wonder if
you think the same is true in humans, you
know, we could imagine that you have a gene
that has, you know, that has a known coffin
of some kind in humans and yet editing it
in one person won't necessarily get the same
outcome as editing in somebody else. And I
think we already know that, you know, just
from observation, that that's true in humans
as well. So I think that's a, that's also
very powerful similarity between what we're
doing in agriculture and what could be true
in humans.
Absolutely. Absolutely.
I mean, I think one of the things that we
tried to, you know, it was a struggle or sort
of a challenge in this film was to sort of,
we didn't want to over-hype things. On the
other hand, we didn't want to give a sense
of just where we are at the moment and you
know, Zach you bring up this question of timescale
and you're right. I mean, and especially with
polygenic traits and how far off that theme,
but we also have many lessons in this film.
There's David Baltimore, who you know,
at the SMR conference, when they're
dealing with talking about recombinant DNA,
none of them ever thought that they would
be in their lifetime, see a tool developed
such as CRISPR. You know, we've seen with
the internet in ways that was a real guiding
principle for us around this film is that,
you know, we've gotten to the point where
the internet is so far entrenched in our lives,
that we didn't have discussions around it
before we sort of thought about potentially
all of its implications.
So I'm curious how each of you looks at this
question of timescale. On the one hand, these
are very, very difficult questions to answer.
There's so much we don't know. On the other
hand, science in some ways goes much faster
or much slower. And I think we're seeing that
in this COVID crisis, you know, people are,
the public is seeing real-time how science
works in terms of steps forward and back and,
and things we think we know. And then we realize
we don't, but yet, you know, CRISPR itself
as a story of, of unknowable speed and precision
and something where nothing could have
been predicted. And then it was, so how do
you, how do you consider that timescale Jennifer?
We used to keep accelerating, at least in
my experience. You know, I think I couldn't
have imagined back when I was a young student
in just learning about biology and chemistry
that...I couldn't imagine the foot race
reaction at that time. Now that's a technology
that, you know, for those of you that are
familiar with it, you know, it sounds kind
of old fashioned and it's woven into essentially
everything that we do. It's actually the fundamental
technology that's, one of them that's being
used right now for coronavirus detection,
for example. And you know, I think same with
with CRISPR. None of us could have imagined
that nature had evolved a system like this
and then we discovered and harnessed for,
you know, you know, mapping and yet where
we are. And so when I try to imagine where
this is all going, and you know, what's going
to happen 10 or 20 years from now, it's difficult
to really predict because I think, you know,
things seem to move at an increasing speed
in terms of advancements. I'll just add that.
I think one thing that is definitely happening
happening right now, and I don't really have
a handle on where it's headed, but I think
it could be really, again, transformational
is the convergence of different kinds of technologies
and not just biological technologies, but
let's say computing technologies, you know,
lots of excitement about the interface between
biology and computing and yeah, I haven't
met anybody yet that really has a clear vision
for where that's headed. We just all have
a sense that there are enormous opportunities.
Also, I want to follow on another convergence here that's raised in one of the questions and that's
the convergence between between the science
and business. I mean, obviously this is a
technology that has gone from the lab to the
boardroom. So to speak in a, at a speed
that's been tremendous, I think around genome
editing in particular, especially in agriculture
raised, there's a lot of questions about where,
why and how the public has had this complicated
relationship. Some of it may be tied around
the role of big business or business practices.
A lot of people push back on that. It's overly
simplistic. How does, how does the business
environment affect where we are? As soon as you talk about business, you're all obviously
also talking about government. And so this
is clearly a technology that is already out
there in the commercial space. Maybe not applicable
yet in many forms, but there's clearly a lot
of investment in this. How does, what role
does big business or for that matter of startups,
small business play with this,
with CRISPR?
Well, I think to answer that I may have to
go a little bit off on a tangent if I may, Elliot
Anytime.
Because I don't, I don't think
it's just about business. I think it's about
the relationship between business and the
scientific community. And I want to be
very careful in how I say this, but in the
1980s, there was a real sea change in which
the, Bayh-Dole act allowed scientists and the
universities to retain the intellectual property
rights to discoveries, even when they had
been financed with public money. And this
had tremendous payoffs in the form of many
of those startups that you're talking about
because unlike the government, private sector
had much more flexibility was much more nimble,
much more motivated to take these lab discoveries
and turn them into something that was worth
something to industry or to consumers. So
we have this explosion of interest in developing
products that might otherwise never have been
developed.
The discoveries would have been of interest
scientifically, but they wouldn't have gone
toward a product or a process, an industrial
process. But at the same time, because of
that scientists that used to be viewed in
that kind of, you know, Martin Arrowsmith
from the Sinclair Lewis novel as the kind
of white hat self-sacrificing martyrs to science
pure, you can trust them. Suddenly, we're now
tainted by the allegation of a conflict of
interest because now they look to make money
out of this. And so it allowed for suspicion
to grow around the statements that the scientific
community made about the value of certain
technologies or the safety of them, or the
integrity of the studies that purported to
show that they were safe, which is what happened
in the area of genetically engineered crops
and the many, many, many studies showing that
there's no known problem being dismissed out
of hand, because there's an assertion that
they're tainted by conflict of interest.
And it's only been exacerbated in recent years
by this growing resistance to expertise and
to government agencies as a source of independent
expertise. So now where do people go for an
authoritative voice? We have an explosion
on the internet of things that sound authoritative.
They have great titles to their pseudo journals
or their websites. And it's very easy for
people to get terrible information and not
even realize that they're getting it from
a completely flimflam source. So I see a challenge here for us, and
I'm not saying we should get business out
of the science because of the benefits it's
brought us, but we do need to figure out how
to regain public trust. And that would be
an important first step.
I mean, hopefully that's what I mean. That
was one of the inspirations for this film
and our larger effort at the Wonder Collaborative
is really try to rethink because not only, you know, flimflam sources, but there's,
there's so much complexity around this, that,
and having worked in journalism and seeing
even how it's covered in journalism. And I'd
say the lack of... the problems often don't some
around necessarily getting the quote unquote
facts, right? I think there's that science
is by its nature... there's
a culture to science and that culture is poorly
understood. Most journalists, even the ones
who cover it, haven't worked in labs. I mean,
I mean, I, my father's assigned to, so I grew
up around it, but I think that one of
the issues that we're seeing, with
the COVID-19 coverage, even in the press,
is a real misunderstanding about how science
works, the incentives around science.
You know, that people can get things wrong
in good faith, that first answers,
you know, we have incomplete knowledge. And
I would really, I mean, one of the things
we try to capture in this film is to try to
put a marker down with the public. And a lot
of the distributors around public, the public
would think, Oh, the public's not interested,
or you can't make it complex. You can't make
it nuanced. You can dumb it down. And
I, and this is one of the things I want to,
you know, it really, was so inspiring from
our early conversations with Jennifer was
that, you know, you refuse to do that. I think
you've been lauded rightfully for your, the
power of communication and the importance
you place on communication. But I would say
it really must start with a respect for the
public that you know, that you, that you feel.
And I think others and hopefully, and that
people that were profile in the film, I think
all came together and believe, look, we should,
we should lay it out there. And I,
you know, we're, we're very excited. I mean,
I'll give a plug for the film. It's going
to be on Nova on September 9th at 8:00 PM,
a special two hour Nova. It's going to be
on Netflix on October 1st. And so, you know,
we've played film festivals around the
world. I really do think that there's a good
news story, that if you treat the public with
respect and you trust the public,
the public can actually deal with very complex
science. So maybe, you know, Jennifer,
there is a question about how did you get
to be such a wonderful speaker about science,
Maybe to get at that, how do you approach
communicating this topic to the public? What,
is your...when you think about messaging,
do you have any certain guidelines that have
driven you in terms of the way you talk about
it?
Well, again, it starts with, for me with
a little reminiscence from graduate school.
So my parents came to visit me in Boston,
and I was so excited to show them what have
you. And I was just so excited about my research
and what I was doing. It was
all new for me. And I just thought they were
just, my parents would just, I think this
was great. So I brought them to the laboratory.
And the first thing that happened was that
my parents said it really smells bad in here.
I realized no it's because we grow e.coli bacteria all
the time, and it didn't smell very good but I didn't notice it anymore.
And that didn't phase me all. I was my, you
know, it was my work environment every day.
And then, so my parents wanted to know,
well, you know, so what do you, what do
you do all day?
And I said, well, you know, I'm studying this
really important problem. It's about, I'm
trying to understand the molecules that might
have led to the origin of life. It was interesting.
And they said, well, how do you do experiments?
Do you, do you see that? How do you see the
the molecules? And I said, well, we don't see them.
Molecules are in these little droplets
of liquid. And we test for their
presence, you know, using different kinds
of chemical types of tests. And so my mom
looked at me and said, you spend all day moving
droplets of clear liquid from one tube to another? And I realize that yeah
So, you know, if there's a lesson there, it
really, it really brought home to me that,
you know, if you want, I just thought I was,
I was over the moon about what I was doing,
but I was so far down into me, I had to really
pull myself back and remember, what was it
like the very first time I went into a lab,
you know, and saw what people were doing and,
and how did they explained to me why does this
matter and how do they actually understand
their data? And so at some level I've
been, you know, kind of working on that problem
ever since. I mean, it's a, it's a big challenge
for scientists because the further you go
in your field, and I think all of us here
are familiar with this, the more we're in
our language, you know, we have our own acronyms.
And when we talked to each other at meetings
and you know, we have to really pull
ourselves back from that and, and try to remember,
you know, what was it like when you were learning
something for the first time? And I guess
the other thing that's helped me a lot is
that I've had the great pleasure to be involved
a number of organizations like the Packard
Foundation, the Pew Charitable Trust. These
are organizations that fund scientists in
a variety of different disciplines. And so
when you go to those meetings, yes, it's all
science, but everybody has to, at some level
communicate their work and why it matters
to people who are not specialists. And that
has helped a lot because, you know, you can
see how other people do it. Some people are
better at it than others. And, I've tried
to, you know, learn from people who are really,
really good at science communication. And
there, there are people out there that are
really very, very good at it. I think the
more that we can encourage our own students
as much as possible. I tell my own students
is everybody should have, we should have a
one sentence answer to the question, you know,
what are you working on? That kind of communicates
what it is and why we should care.
Well, Zach, I will try not to use what Jennifer used
"to be down in the weeds" I'll try not to use
that as a segue to your work, but, you know,
in some ways your lab, well, part of it
looks like what your backdrop is, which is
a very different environment, but how do you,
in some ways people have a much more familiarity,
you're not necessarily moving clear liquids
around, although at some level you're also
doing the very same thing. How do you view
communicating science? And I think it's important
with Jennifer mentioned, for scientists. Once
they get out of their own specialized field,
often communicating to their peers doesn't have to be that different in
some ways in the general public. But how do
you, how do you talk about your research?
What approach do you take for that?
I really look at it from the perspective of
what still gets me excited. So I'm excited
to walk down the field, look at these plants,
see these trait variations, and then think
about the chromosomes and the genes and everything
that's happening happening in terms of how
Mendel and what we learned from Mendel's peas
is now happening with genome editing and
what we're doing. So my communication, which
actually did quite a bit with elementary school
students and middle school students, is to
just show them how cool science is. I mean,
really, I know it sounds trite, but it really
is very cool. And the more I can bring them
to that level of understanding of how cool
it is, I think it's much easier for me to
get them excited about some of the nuances
that maybe they would be bored by in the classroom.
So for me, it's always about trying to talk
to them in a way that gets them excited about
what's really innovative and cool about science
and biology overall. And that seems to work
pretty well. At least it works with my kids,
most of them anyway.
We just have a couple
more minutes, Alta but you know, you, you're a
wonderful communicator yourself. How do you,
and, you know, then their communication,
the film was vital for it, really giving a
sense
of this technology and where the limits are.
How do you, how do you view your own role
in communicating?
I spend a lot of time doing exactly what
Jennifer was talking about. Know your audience,
talk to people about what they want to talk
about. And then you can throw in the stuff
that you find really interesting that they
may not have thought about yet. And they may
come along with you if there's real passion
and real enthusiasm and the way you address
it. But you have to start by talking to people
about what they are interested in, as
opposed to just scolding them and telling
me what they ought to be interested in, what
you think is cool, but I couldn't agree more
with you Zach. It's because of the
cool factor that we can get people to want
to explore this out of curiosity and out of
wonder.
Well, thank you. And that's a wonderful plug
for our Wonder Collaborative, and that's the
reason why we called it that production behind
this film. And I wanna thank all the panelists
for joining us and Cold Spring Harbor Laboratory
for hosting this. Once again, I hope you enjoyed
this discussion and Human Nature. As I mentioned
it's going to be viewed on Nova on September
9th at 8:00 PM, and also then
hit Netflix on October 1st. So please watch
it. The more people that watch it and believe
in this kind of science storytelling, the
more hopefully others will invest in it. And
let us do more projects like this.
