Evolution, the natural process that shaped
all life, and can lead from this to this.
It's driven by random genetic mutation and
natural selection.
Random mutations create variation.
Sometimes a change gives an advantage, like
cells that can detect light to help seek out
safer environments.
Survivors pass along the changes to future
generations, further changes can occur over
many generations and sometimes hundreds of
millions of years.
Fast forward to today.
Now we have molecular tools that can allow
us to alter the direction that life takes,
including our own.
The most accurate and effective tool yet for
gene editing is called CRISPR.
We can use it to essentially rewrite any gene,
however we choose.
Potentially fixing mutations that cause disease.
The most common analogy for how CRISPR works
is the find and replace function of a word
processor.
And with CRISPR, what used to take nature
millions of years can now be done in a lab
in just days.
It is a groundbreaking tool with unprecedented
power.
It shows promise for curing cancers, ALS,
and many other diseases.
We've already engineered malaria proof mosquitoes
and may create mice immune to Lyme disease.
But possessing the power to forever alter
the future of life raises difficult questions.
What could justify genetically modifying the
ecology around us?
Should we move beyond curing diseases to making
other genetic enhancements?
Are there any lines we shouldn't cross?
How can we avoid the misuse of this powerful
technology and can humanity even agree on
the future of our very own genetic destiny.
Tonight we're going to hear from a range of
experts working on different aspects of CRISPR,
which stands for Cultured Regularly Interspaced
Short Palindromic Repeats.
Wow.
But we are not going to let that scare us,
are we?.
No.
So allow me to introduce our distinguished
panel.
Josephine Johnston is a bioethicist and lawyer
and the Hastings center.
She works on the ethics of emerging biotechnologies
with a focus on their use in reproduction,
psychiatry, genetics and neuroscience.
So please welcome Josephine Johnston
He's a member of US National Academy of Sciences
and has served on several national research
committees studying the environmental and
health effects of the commercialization of
genetically engineered crops.
Please say hello to Fred Gould.
Samuel Sternberg is an assistant professor
in the Department of Biochemistry and Molecular
Biophysicists at Columbia University.
He is the coauthor with Jennifer Downer of
A Crack in Creation: The Unthinkable Power
to Control Evolution.
Sam Sternberg.
Neville Sanjana is on the Faculty of The New
York Genome Center and assistant professor
in the departments of biology and neuroscience
and physiology at New York University.
Neville Sanjana.
So first we're going to start with an overview
of the great potential of this technology
CRISPR in terms of human diseases.
Research is underway on a number of conditions.
And I'm just going to throw it first off to
Neville right away.
Don't be surprised.
Just tell us what the range of diseases is
that CRISPR has a potential to cure.
Yes.
So I think in the last few years it's had
just a huge impact across biomedical science,
and some of the diseases are very common diseases.
What lot of us know folks who have cancer,
cancer's like skin cancer, lung cancer, blood
cancers.
There's also a lot of non cancer applications.
I think with CRISPR too, blood diseases like
sickle cell anemia or Beta thalassemia and
other diseases that are being worked on right
now with CRISPR or some eye diseases, some
diseases of the retina that result in blindness.
So I know that there's been a lot of research
on mice and monkeys, but none of this has
applied to humans yet.
Has it?
There are clinical trials either underway
depending on ... in some countries already
underway and definitely in advanced planning
stages in US and Europe and China.
I heard the China actually did use CRISPR
for an eye disease, right?
On one person.
Do we know what the outcome was?
I don't think that's been published yet.
But there's actually a number of clinical
trials for cancer that have started in China
where you use CRISPR to edit immune cells
that actually get delivered back into patients
to hunt down cancerous cells of the body.
So I don't think it's too early to say how
effective these treatments are going to be,
but there's a lot of hope, I think, across
the scientific community that there's kind
of this new age of precision medicine using
gene editing to treat some of these more common
genetic diseases or cancers in a fundamentally
new way.
Wow.
So Fred, just as an overview, just to start
the whole discussion, tell us about CRISPR's
potential in plants and animals.
Yeah, well, especially in plants there's a
possibility of using CRISPR to change the
genetic composition of some of our crop plants
to make it more resistant to plant diseases.
And that could decrease use of insecticides
or herbicides and also fungicides and so on.
So that's been a very important possible contribution.
And with animals, the hornless cow that was
recently produced, you know the idea that-
The what?
Yeah.
So, well, bulls will have horns and typically
you have to do sort of a surgical operation
to get rid of the horn.
So the idea that you could engineer these
cattle not to have horns, is something that
has been done by regular breeding but could
also be done using those things.
But a lot of these things are just starting
to be considered and are not actually on the
market yet.
I did a story on 60 minutes about 10 years
ago on a program to bring back extinct animals.
And I've read the CRISPR may be used in that
kind of an effort.
Sam?
Yes.
There's a famous geneticist at Harvard, George
Church, who's been in the news a bunch of
times.
I think there's a book that's coming out or
has come out, Using CRISPR to Resurrect Wooly
Mammoths.
Now, we had a discussion earlier how realistic
is that actually.
I would still put it personally in the box
of science fiction, but the point is we actually
... scientists have decoded the entire genetic
sequence of the wooly Mammoth from fossil
samples, from preserved specimens.
And you can compare the Asian elephant genome
and the wooly mammoth genome, pinpoint all
of the precise DNA changes between the two
and now use this powerful gene editing technology
to actually go into Asian elephant cells and
start changing individual genes one at a time
from the version that modern day elephants
have to the version that wooly mammoths once
had.
And then the elephant would give birth, right?
Well that's the part that I think no one's
worked out IVF in an elephant.
The gestation time of elephants is like two
years.
That's the big question.
Could you ever actually give birth to something
that even resembled the wooly mammoth?
I'd say not in my lifetime, I would guess.
But if you read the news stories about it,
people say five, 10 years, you'll see something
being done in that area.
Josephine, just as an overview, what are some
of the negative aspects of this, as a bioethicist?
Well, the first thing I would say is I think
because it's a platform technology with so
many different uses, it's not sort of just
a good or a bad technology and the uses really
vary.
But people who are speaking about some of
the concerns that they might have across these
different potential uses are concerned about
a real range of things from safety type questions
about like how would we know ... could people
create sort of weapons out of using these
technologies.
That's one sort of really sort of ... very
clearly dangerous and potentially frightening
scenarios.
And that people are looking at all the way
across to questions around how appropriate
it is for humans to have such a lot of control
over the genes of ourselves, our children
or animals and to what ends, like what are
we pursuing, what's the purpose of it?
So there are a lot of questions raised right
across those different uses.
And as we move forward, we'll be discussing
the pros and cons.
So we set the stage, but let's go back in
history a little bit and talk about all the
different ways that we were manipulating evolution
and our genes before CRISPR, and for good
or bad.
So Fred, start out with us on me plants and
the manipulation of plant genetics?
Right.
So I think that many of you probably do know
that your plants didn't just arise from nowhere,
they were almost all bred by farmers and by
technicians over thousands of years.
And so we often use the example of teosinte,
which is sort of a weed that grows in Mexico
with a very small seedpod.
And that has been over time changed by farmers
who have just selected the best plants that
had the most nutrition over time to bigger
and bigger corn.
And today we have modern corn as a result
of that.
So we also have the same thing with our animals,
both in terms of farm animals, but also think
about your dogs and cats.
Think about the odd goldfish you can buy in
a store.
We've manipulated animals and plants for a
long period of time.
And what about food?
Who wants to tackle food?
Okay, Fred, come back-
Yeah, I'll come back to food.
... tell us what we're eating.
Sure.
I mean, genetically modified today?
Yeah.
So I think it's very genetically modified.
Okay.
So I just told you about Teosinte being bred
to become the modern day corn plant that is
genetically modified from teosinte.
But when people talk typically about genetically
modified or GMOs, they're talking about something
that has been engineered.
And we have to talk about the difference between
that.
I think a lot of it goes back to a cultural
thing about what is natural and what is not
natural.
And it's natural to just save seeds that are
better and better and move ahead.
Most people will say that is natural, but
they wouldn't say that it's natural to take
cells out of a plant and insert DNA in them
to make them different.
And so we have about 80 to 90% of our corn,
soybean and cotton in the United States has
been developed that way.
Genetically modified?
Genetically engineered.
And I like to use the term genetically engineered
because it's engineering, in the sense that
it's actually thinking about an architectural
plan of a plant and changing it, as opposed
to something that you just do tinkering with
it, as some people would say.
So that's a big change in terms of how people
relate to something that's been developed
those different ways.
And to go back and say that, what's the difference
between a plant that has the same characteristics?
Let's say you change a corn plant from being
yellow to being blue based on conventional
breeding, like the folks in Mexico have done,
but then you do the same thing using genetic
engineering.
Is that different?
Would you accept it more if it was done one
way versus the other?
Well, what do you think?
I think people respond very strongly because
of cultural values.
And actually there was a map of where these
engineered crops are grown.
In the United States, we grew about 10 or
more different genetically engineered crops.
In Mexico, they grow genetically engineered
soybeans and genetically engineered cotton,
but they don't allow genetically engineered
maize or corn because that's sacred to them.
If you look at Diego Rivera's paintings, corn
is a main sacred object.
So under those kinds of conditions, there's
a cultural thing against having something
that's been built artificially.
And there's a good map right there.
That's a map that's telling us where GMOs
or genetically engineered crops are, what,
accepted?
Where they're grown commercially within the
legal framework of regulation.
And China's a very good example where they
have almost a hundred percent genetically
engineered cotton.
But in terms of legally grown rice, there's
0% genetically engineered rice.
And it sometimes surprises people in a top
down supposed society, the government would
like to have genetic engineering, but they
have a very big green peace movement in China,
surprises Americans, and that they don't trust
that their rice would be safe if it was genetically
engineered.
Josephine, do you think this tampering, tinkering,
modifying nature is part of human nature?
Have we been always doing it as long as there's
been a recording of what we've done?
Yeah, probably.
That doesn't really tell us if it's good or
bad.
There are lots of things we have been doing
for centuries if not millennia that are good
and some of them are also not good.
So there were a lot of things that we do naturally
and they may or may not be good.
Good or bad may depend on your culture.
Yeah.
And it could also depends.
I mean there were a lot of ... some of the
interesting differences, I guess, between
those two different ways of getting blue corn
are also to do with the timeframe, the speed,
the ability to look at something developing
in concert with its surroundings.
That when you speed something up, you may
or may not also miss certain aspects of it.
So there are many things I think that people
are objecting to when they raise concerns
about genetically modified foods and safety
is maybe one of them, but there are also issues
around who controls the food supply, having
a limited diversity of crops ultimately, whether
or not there are certain companies who then
have a lot of power over things that farmers
have actually been doing for centuries their
own way.
So there were a lot of other issues in there,
I think, also around trust that are not just
represented by concerns about safety.
Sam, jump up to the 70s and 80s into the modern
era of genetic technology.
And what were the tools that were used after
we understood more about the genome, before
CRISPR?
GC, Before CRISPR.
So Fred just brought up GMO or genetically
engineered foods and the kinds of crops we
have like corn, rice, these other ones, those
were using recombinant DNA.
So in the 70s there was this revolution where
researchers developed a set of tools that
they could use to piece together bits of DNA
in test tubes.
So it was the first time that you could really
isolate specific genes, you could package
them in different ways and you could actually
introduce that genetic material into coli
for designer bacterial strains, into plants,
into animals.
You could make genetically engineered mice
because of this ability to manipulate DNA
inside of a laboratory.
Now, it's not the same precision for making
changes that we might have today, but Neville,
I think you were going to talk about this
picture that these are some ways that you
developed yourself, Huh?
I think these-
Is this pre CRISPR?
These are not mice I developed myself.
These are mice that have a protein from jellyfish.
So jelly fish, many species of jellyfish have
this naturally produce this green fluorescent
protein.
And so these mice were developed to be able
to visualize different cells.
So we were using them to actually look to
see how the axons of neurons grow, this was
during my PHD work, and find their neighbors
and connect up in the brain.
And so it's very nice to be able to visualize
these with this green fluorescent protein.
And so this is-
So they glowed in the dark?
They can glow in black lights, exactly.
So they're party mice, but they're very useful
for science.
And how did you do it?
So this was done by a Japanese group that
introduced, not in the CRISPR era, but randomly
introduced this trans-gene.
We call it a trans-gene because it comes originally
from a different species, from a jellyfish
randomly into the mouse genome.
It sounds, doesn't sound, I read that even
with CRISPR, but we're going to stay away
from that, even with CRISPR that all the discoveries
have come because you've studied nature and
you've looked at what nature had done and
then you build on that.
So the basis of both what you're talking about
and CRISPR comes from observing the way nature
would move forward.
Is that correct?
That's why being a bioengineer, and I mean
Sam can talk to this too, but why being a
bioengineer I think is so exciting.
Yeah, I mean it's self justifying my career
choice, but it's fun because there's so much
inspiration, I think, in nature.
And so many useful tools have been created
over a millennia of evolution on this planet.
And I think the tool that we're talking about
today, CRISPR and other tools are ... it's
an exciting thing to do, to be able to see
these working in one context in nature and
then try and use them perhaps translationally
for medicine or for plants.
So as we come up to today, with all the fears
that people have about GMOs and the kind of
cross-breeding's and the things you're talking
about, have any of the fears have been realized?
why is the public so against GMOs?
I think that probably people have
different reasons that they're concerned.
I do think that the safety of them just to
eat hasn't been explored or explained adequately.
But it's been around for a long time, right?
I would say, so we have been eating genetically
engineered corn in the United States since
1996, so we've had quite a few years of eating
that genetically engineered corn.
But the question is how would you know if
it was doing something?
And I would just say ... I spent quite a while
chairing a committee with the National Academies
looking at the safety and looking at the testing
that was done.
As many of you have probably seen newspapers
or on the Internet of these rats with big
tumors and things.
But looking through those-
From GMOs?
Yeah, from GMOs.
I mean it's something that cruises around
the Internet all the time, but when you look
at it carefully, not all the tests that have
been done have been appropriate or powerful
enough to say if there's a small difference.
But if you take all the testing that's been
done over this long period of time, there's
no evidence at all that has emerged either
from the actual animal testing or even ... we
did a comparison of people who live in the
US and Canada where GMOs are prevalent, to
people who live in the UK or the EU, where
they haven't been, to ask these questions
about whether chronic diseases have increased
in the US and Canada than what you see in
the EU and the UK.
And when you look at the numbers of things,
everywhere from diabetes to cancer, different
kinds of cancer-
Obesity.
You don't see any change different in the
US and Canada compared to the EU and the UK.
Now somebody could say, well that hasn't been
a long enough period of time, but science
is always that way.
I think probably many of you know that if
you live long enough, you find out that eggs
are good or bad or salt, you should have this
much or that much, science changes.
But I think that no really strong acute changes
have occurred based on countries where they
eat GMOs.
How CRISPR came to be.
The creation story is an amazing one, made
possible by the work of many labs all around
the world.
So my first question at this stage is how
does it work.
And we're gonna watch a short premier that
was produced by one of the CRISPR pioneers,
Jennifer Doudna is going to teach us how it
works.
CRISPR is a technology for changing the sequence
of DNA in cells in a precise fashion to correct
mutations that might otherwise cause disease.
So scientists can actually change an individual
base pair in the more than 3 billion base
pairs in a human cell.
The Fun thing about the CRISPR technology
for me is that this is a project that started
off as a basic science curiosity driven project.
It was a collaboration between my lab, and
the lab of Emmanuelle Charpentier.
We teamed up to discover the function of the
protein Cas9 and how it acts to disrupt viral
DNA in bacteria that have a viral infection.
We came to understand the way that Cas9 is
programmed by RNA molecules in bacteria to
recognize specific DNA sequences and then
make a break in the DNA.
We figured out that we could actually program
Cas9 to cut any DNA sequence by redesigning
the way the guide RNA and the protein is being
used in cells.
That understanding led to really the Aha moment
realizing that this could be actually a very
powerful technology in animal and plant cells.
It's very exciting because it's going to enable
a lot of science to be done that was impossible
to do in
the past.
I always like to stress that there's CRISPR
technology, which is what we think of when
we talk about gene editing, making these genetic
changes in human cells and plants, animals.
But what got us all interested in CRISPR in
the first place was this fundamental question
she just talked about, which has nothing to
do with higher organisms, but just bacteria.
And thinking about how bacteria can stay healthy
when they're growing in the soil, in the human
gut.
Every place that bacteria reside, they're
actually being constantly bombarded by viruses.
And these bacterial viruses are the most prevalent
form of life on earth actually.
They outnumber even the grains of sand on
the planet.
There are more viral particles that infect
bacteria.
And so this is big question , how do bacteria
protect themselves?
And it's been known since the middle of the
20th century that they have innate immune
system, much like humans do, but what a number
of different research groups discovered in
the mid 2000s is that they have this other
form of immunity called CRISPR, which uses
a pair of molecular scissors.
So this kind of oversimplified schematic on
the slide where they actually recognize DNA
from a virus during an infection, and they
slice it in half and that leads to the viral
genome or the viral genetic code being destroyed,
and the bacteria can survive the infection.
So CRISPR, is that also called CRISPR?
Yeah, CRISPR has kind of become this umbrella
term.
Really what it refers to is the overall immune
system, but the star player that's now transformed
gene editing technology is a particular enzyme
called Cas9.
And the Cas is actually an acronym that comes
from CRISPR associated.
So Cas9 is not a bacteria?
It's a bacterial enzyme.
So protein molecule, one specific protein
that some bacteria produce.
And actually the genesis story was done in
a bacterium called streptococcus thermophilus.
You eat it every day you have a bowl of yogurt.
So it's the main workhorse to ferment milk
into yogurt and other dairy products.
And it was a company that was trying to make
these bacterial fermentation cultures more
virus resistant that led to the discovery
of CRISPR actually.
So every time you eat yogurt, you're eating
CRISPR actually.
But it was a discovery that you can take these
specific pieces out of those bacteria and
put them in a human cell or a plant cell or
an animal cell that led to this revolution
in gene editing.
To me, it's really fascinating.
I think you mentioned this, but it's worth
stressing this, that this is an adaptive immune
system in bacteria.
Bacteria are tiny single celled organisms.
We're these, whatever, trillions of interacting
cells that make us up.
And we have an adaptive immune system.
We know we have antibodies and we have T-cells
that fight off infections.
But that's because we have so many cells.
But to me, it's just mind blowing still that
a single cell, a tiny one celled organism
has an adaptive immune system.
That word adaptive means it can have a memory
of previous invaders, previous viruses that
it's encountered, which it keeps in this CRISPR
area of its genome.
And when it sees something that matches that
memory, as Sam said, it's a molecular scissor,
it can cut it and get rid of it before it
harms and sickens the bacteria.
It's very cool.
Let's do a round, and we'll start with Neville
and come all the way around.
Tell us in your own, and from your own perspective,
in your own words, what you think is so revolutionary
about CRISPR.
Oh, okay.
That's a good question.
What's so revolutionary about CRISPR?
Yeah, I mean, it's kind of hard I think to
overstate what it's enabled us to do.
So basically one thing that we as biologists
and geneticists have been limited in some
ways is we have this concept in biology of
a genetic model organism.
So you might hear a lot of studies that involve
either bacteria or fruit flies or mice.
And you might wonder, well, why do scientists
just love these couple organisms that I keep
hearing about?
Why do I hear so much about mice but not about
rats?
Is it just that mice are cuter and scientists
like using cute animals?
There's a reason actually that they've, um,
kind of fixated on a few different organisms.
And that's because those are genetic model
organisms, meaning their genomes have been
easier to manipulate, so we can understand
what changes in their DNA in their genetic
code what they do to those animals.
We can understand the connection between the
DNA, the genotype and the phenotype; how it
looks to us, how the animal behaves.
And that's been the case up until very, very
recently.
And I think one of the real breakthroughs
in the CRISPR era is the idea of the genetic
model organism is very different now because
everything, it can be a genetic model organism,
including what a lot of people consider the
most important organism or model organism,
which is us.
We'd like to study something to understand
about how our genes result in maybe diseases
that we get are and how we can repair hose
defects.
And so human cells, the DNA was actually quite
hard to manipulate until recently.
And really any organism now is a genetic model
organism with CRISPR.
I'm supposed to follow that?
Yeah
I went on too long.
Can I just pass and say, that too?
I agree with that.
I guess for me, I mean I love you're wondering
about how does this work because that's what's
gotten me excited is really the mechanics
of the whole process.
I think what is often unappreciated about
even CRISPR is that it's become a moving target
because there's no one thing that defines
CRISPR because what we've discovered over
the last 10 years or so is that there are
all different flavors of CRISPR where the
Cas9 protein that we've been talking about
isn't even present where different strains
or different groups of bacteria have evolved
different types of enzymes that might work
similarly, but do completely different things.
Or we're not even edit DNA, but edit RNA.
And one thing that a lot of researchers are
doing now is continuing to harness nature
and kind of remain inspired by what bacteria
and other microorganisms have evolved to be
able to do over evolutionary time.
And then think about how can we re-engineer
their system and use it in more creative ways
to solve problems.
Okay.
Good
I'm up next.
All right.
Okay.
So here we go.
So we'll take this to a higher level.
That was pretty high, Fred.
Fred, can you bring it to a lower level please.
All right, so I study insects and we're concerned
specifically about agricultural insects, pests
on crops, but also mosquitoes that transmit
diseases, and one of the most talked about
is malaria.
And when we think about using CRISPR to decrease
disease, sometimes we're thinking about manipulating
human so they won't get the diseases and so
on.
But with something like malaria that is transmitted
by a mosquito, people have been working for
many years with transgenic mosquitoes where
you've changed the genes to make it so the
mosquito can't transmit malaria.
Now it sounds really good, but think about
it.
If you release a couple of thousand mosquitoes
that you've bred in the lab, they're going
to be millions of other mosquitoes that do
transmit the disease.
So what we've been working towards for a long
time is a way to get those genes to move into
the population based on being inherited more
than expectations by Mendelian inheritance,
so that it'll push the gene into the population.
And people have worked for a long time and
how to do that.
And what has happened with this CRISPR technology
that came from the biomedical researchers
was this recognition that what they're trying
to do is put the gene into an organism and
have it function.
But that's just a one off thing.
And the idea is that once you put that gene
in, you can use different manipulations so
that it automatically continues to put itself
into new organisms.
So when you give birth, all of your offspring
will have those genes instead of half of them.
So if you think about linking that with a
gene for not transmitting malaria, all of
a sudden that mosquito population becomes
a nuisance, but not something that's transmitting
malaria.
So that's exciting.
That's really exciting.
In my lifetime, this is the first time I've
had a ... in my lifetime that we've actually
seem to have the means not just to select
the genes are future generations, but to actually
change them.
And so that's monumental prospect.
It doesn't anything someone's doing right
now that we know about, but it's certainly
like dangling there as a much more real prospect.
So decades of people thinking about being
able to do something like that to actually
potentially being able to do it, that is monumental.
And the other thing that's come along with
that I think was this really, I think, brave
and really important move that Jennifer Doudna
and other people involved in the development
of the technology made, which was immediately
asking for an international conversation about
that potential.
So that moment of open science and raising
questions about your own work and acknowledging
that you, the scientists, are looking for
everyone else to join in the conversation,
that's a monumental moment as well.
I want to move us though into the whole question
about genetic changes in the human body and
medicine.
And so let's divide this up, first let's talk
about non-heritable diseases and then we'll
talk about heritable.
So non-inheritable diseases, some cancers,
some blindness.
What benefits does CRISPR offer over the earlier
technologies in this whole area of non-heritable?
Sam or Neville, either one of you.
Sure.
I don't know if I'll address the non-heritable
part exactly.
I think the key ... I mean, we talked about
this earlier, but really the key property
has been the easy programmability that this
is really getting into the realm of almost
like programming a computer.
It's something that we can do, except we do
it in the lab, but quite easily.
And so it's enabled us to ask questions really
of a different scale.
So in previous decades, you'd often have a
geneticist who spent their entire career working
really just closely focusing on one gene and
really exploring what happens where that gene
is maybe mutated or has other changes to it,
or what patients with conditions that involve
that gene look like.
But here with this easy programmability, we
can now, a single investigator, a single scientist
can actually ask really genome wide questions.
They can say of all 20,000 genes in the genome,
that's how many genes are in the human genome,
what are the effects of each of these genes
on the growth of a cancer cell or on resistance
to a cancer therapy?
And so that's some of the work that we've
been doing in my lab.
And you can ask all the genes at the same
time?
All the genes at the same time.
A single scientist.
And that's really an unprecedented scale where
we can develop libraries of CRISPRs each with
a different guide RNA, this component that
Sam mentioned that programs, the Cas9 or other
CRISPR enzyme to go to different places in
the genome.
A library of guide RNA that target all of
the 20,000 genes in the genome.
And then we can have this pool of cells.
And this is again, human cells.
This is the model organism we care about in
biomedical disease science.
And have this pool of cells and then say,
which of these cells now are resistant to
a drug that they shouldn't be?
And okay, maybe this gene, if we see a patient
with a mutation in this gene, we now know
we shouldn't give them this drug, we can predict
in advance of when they come into the clinic
that this might trigger resistance.
These are the kind of ... we're not quite
there yet, but this is where this is heading.
Well let's say I have cancer and we're at
the stage where CRISPR is ready to help me.
So how do you administer or how will we administer
CRISPR changed medicines?
Is it IV?
I think it's impossible to predict the future,
and in this field is changing rapidly.
But I think we have a clue by the clinical
trials that are just being registered right
now, and a lot of them involve taking advantage
of the immune system.
That's been a huge transformation in cancer
therapy over the last decade is the introduction
of immunotherapy, first in clinical trials
and now in many FDA approved medicines, that
encourage the immune system to fight cancer.
And so instead of administering drugs or antibodies
on a continual basis, there's the idea of
taking out a small portion of cells using
gene editing to modify those immune cells,
and then having something that would not require
continuous administration, maybe it would
be administered just once.
These are the trials that are starting now
with gene editing.
On humans?
On humans.
Maybe I could talk about one example, it's
actually, as far as I understand, the first
clinical trial using gene editing in the pre
CRISPR day.
So it's a different platform, but same basic
concept for HIV positive patients.
And the way this clinical trial was administered
is patients have immune cells removed from
their blood there then edited at a particular
gene that's been known for decades to confer
resistance to HIV viral infection.
So the idea is you actually take a patient's
own cells, you transform them into cells that
can no longer be infected by the virus, but
they're otherwise still the patient's own
cells.
So it's not coming from a donor where you
have to worry about immuno compatibility.
You edit the patient's own cells and then
you deliver them back into the patient's bloodstream
where hopefully those cells will take hold
and now generate a new reservoir of the patients
edited cells that have HIV resistance, and
will pass on that resistance to all cells
that end up coming from cell divisions.
And if you can hit the stem cells, even better
because now they're going to have an immortalized
permanent line of cells in their body that
had been edited and can never be infected
by HIV.
What's amazing about this is there's actually
people that carry this mutation naturally.
There's a few very, very lucky individuals
that are basically immune to HIV.
And it's through studying the basic disease
mechanisms of individuals that we now know
what gene could be targeted in the rest of
us to have HIV immune cells.
This technology has been offered in an open
source way, so it is available for scientists,
am I wrong about this, all around the world,
any lab, unscrupulous people or not, it's
even offered on the web.
You can buy a CRISPR kit today online.
So is the horse out of the barn or can we
get something, at least a discussion, a serious
way to make sure that things about what you're
talking about doesn't happen, to make sure
some guy isn't making a monster in the basement,
all kinds of possibilities.
And it seems that we're there and we should
have talked about it already.
We should have been regulating it already.
Why is it open source, for example?
I only can say about the open source because
I think the rest of the question is very important
too, but I think in terms of science, there's
some examples where things were a little bit
less open source.
Today it's much easier to share because of
things like the Internet, but previous technologies,
one famous one is PCR, Polymerase Chain Reaction,
which is a very famous technology in molecular
biology, won a Nobel prize.
It allows us to very easily amplify specific
pieces of DNA.
It was created in the mid 80s.
Very powerful technology that was initially
patented by the company that discovered it
and kept in a quite proprietary way.
Now it's widely disseminated.
I think saying it's different about the CRISPR
community in Sam has been a key part of this
too, is that all the labs, a lab that I came
from, Feng Zhang lab really pushed to the
forefront the idea of very quickly putting
these tools in a nonprofit repository called
add gene that would distribute them to any
scientist for a very nominal cost.
I mean, there's some other things you can
focus on too, but one thing that's really
important to bring up is this is unusual in
science, how quickly this has been shared
and it's had an unbelievably positive impact
on allowing biomedical scientists to just
do a lot more and a lot faster than they could
get there.
But who's thinking of the downside?
I'm going to talk about the upside, maybe.
But that's been my experience and it's really
been different than a lot of other science
and it's hard to overstate that actually.
Yeah.
None of the scientists want to talk about
the downside.
I mean, I can say a little bit about the uses
in humans and in embryos and sperm and eggs
and things like that.
But I don't know the answer to these questions
about how it stops somebody from ordering
it over the Internet and using it in an animal
or in a nefarious way.
But through me, when it comes to humans, so
even in ... the US does not have comparatively
in an international sense, doesn't have a
lot of federal regulation that deals with
in vitro fertilization or these reproductive
technologies.
Some other countries like the UK and Canada
and Australia and various other countries
have sort of legislation that regulates and
oversees manipulation of sperm eggs and embryo,
and makes rules what can and can't be done.
And a lot of those countries have laws that
say that you cannot make heritable changes
to human embryos, for instance, or to the
eggs or sperm.
So can't make a change to the genes that will
be passed on.
Now, they might be reconsidering just exactly
how stringently they want to stick to that-
Even if it's positive?
So at this point, yeah.
But just to say that ... in 1990 the UK developed
a regulatory scheme and an oversight system
for looking at all of this.
And right now in the US there is a little
bit of data collected from IVF clinics so
that we have some idea of what's going on
in terms of like how many cycles of IVF are
there and how do they use donor eggs.
Any potential use of these gene editing technologies
to make a baby would have to go through the
FDA.
what about saying you can't make a change
in the embryo?
I think that's something that needs to be
discussed and it is being discussed.
And, I mean, Josephine earlier mentioned,
you know, Jennifer Doudna and a very large
group of scientists, but also non-scientists
importantly have met.
2015, there was an international meeting,
I think there's another one planned for the
end of this year.
And I think that's a critical piece to really
having a broad discussion about what on an
ethical and social level should and shouldn't
be offered.
There are scientific technicalities about
off-target effects and unintended consequences.
But I think there's also a bigger question,
which is what kind of society do we want to
live in and what types of interventions should
be supported when frankly there's a lot of
other social problems in our society that
would be addressed with a lot less money than
might be put into generating genetically edited
babies for a very select few individuals.
So I think whether or not a rider-
But discussing it?
Your community is having conferences to discuss
the ethics and what regulation makes sense.
I mean, I think it's your community.
I mean the National Academy of Sciences of
the US did a whole report on the prospect
of using gene editing in humans, including
to make changes that could be passed on from
one generation to the next.
And in that report, they argued for allowing
potentially some heritable changes, but if
they meet certain really strict criteria.
So I feel sort of steeping a wee bit back
from the idea that we can't make a heritable
change and saying, well maybe we can if we
can show that it's safe and effective and
if it's a disease that's really serious versus
like giving people purple eyes or something.
So like there is a discussion and it's not
just among scientist.
Think about how heritable disease that you
could eliminate from the face of the earth.
I mean that's possible.
That's part of this and why would anybody
try to stop this?
Well, let's say those rare cases where you
have parents that have no other option to
have their own child that will be free of
disease.
No intervention as many cycles of IVF and
genetic screening of embryos, none of that
will allow them to have a child that doesn't
inherit their disease.
You can make a strong argument for if there's
a technology that can address that problem
and we can administer it in a socially responsible
way, should we have some red line that says
no, If you change the DNA of an embryo, that's
wrong, but if you do it in a patient that
lives with the disease, that's okay.
I mean some people might say, Why are we making
this distinction?
We would be okay intervening surgically on
a newborn baby, what's the issue with doing
it earlier in development if it's a genetic
intervention?
And actually that's why the UK recently changed
their law around this issue to allow for something
called mitochondrial replacement technology,
which isn't CRISPR, but it does introduce
a heritable change into the embryo.
And so they had a whole public debate, they
debated it in parliament and they made a change
to their law to allow for this.
So I do think that there are ways in which
regulatory structures can be adaptive to these
really compelling cases without necessarily
just opening the gates.
I'd like to go back to the comment that two
of you made about getting rid of these diseases.
This idea that if you had the ability to get
rid of the scourge, and that sounds like it's
global.
And I guess even if these technologies become
pretty feasible, and I think Sam was bringing
this up, who is going to get to use them?
Are we really going to be able to eliminate
a disease like that that requires us to mess
around with an embryo, even if we're great
at it when we can't even give people enough
to eat.
So who's going to get it and who's not going
to get it?
And that becomes a real important social issue
is to where are you going to go with this
and what else could you use that same money
for in terms of helping society.
So I salute you all.
I hope that we didn't talk over your head
or under.
I hope we hit it just right.
That was our goal.
So I want to thank you all for the work you
do everybody.
Thank you.
