Transcript
E8vi_PdGrKg • The Realities of Gene Editing with CRISPR I NOVA I PBS
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Language: en
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cas9
plasmid grna plasmid the dna
template this is so nuts
the new gene editing tool crispr has
revolutionized
our ability to edit nature so where
exactly is this technology today
and where is it headed next it's time
for a gene editing reality check
i can't wait till kids are playing with
this instead of legos just crispering
bacteria in their bedrooms i literally
ordered an
at-home gene editing crisper kit you can
get anything over the internet this
shipped to me in about four days
now to be clear this crisper kit only
modifies bacteria
but still do not inject yourself with
any of this
this is just what crispr looks like in
the lab
test tubes pipettes plates of cells
but what can crispr do in the real world
i'm dr alok patel a pediatrician
medical journalist co-host of nova's
parentalogic
and host of the podcast nova now which
yeah i record for my closet you can't
tell but i'm surrounded by clothes right
now
i want to find out how crisper is
actually being used
right now and how far away from being
able to edit humans or create designer
babies
is this all science fiction to my
surprise
i found out that i could actually meet a
designer baby
of a slightly different variety
about an hour outside of san francisco
so i'm like really excited to be on this
farm right now
welcome to uc davis i did my absolute
best to put on like a
urban farm look well you got the urban
right
i don't know about those white shoes you
know what cows do right
fair point can we go meet some cows
let's go see cosmo
i'm here to meet cosmo a calf that was
gene edited with crispr as an embryo
to do something surprising to load the
reproductive dice in favor of making
male offspring we will go in here
that's looking for your shoes that's
looking for my shoes that's what she
thinks of you
it's an utter delight to meet you oh god
shall we go down and see if we can speak
to cosmo
so we're gonna see the star of the show
right now right yeah hey cosmo
how's it going cutie pie you're gonna oh
don't run away how you doing dude
sometimes if you just kind of kneel now
why would someone want to make more
boy cattle sounds kind of random but
livestock geneticist allison van impe
explains why this
actually makes sense there are certain
sexes that
are suited for different purposes in
agriculture
in the beef industry the males are more
fuel efficient converting the hay
into beef and so it's basically trying
to improve the efficiency of beef
production
today cattle grown for beef contribute a
lot
of greenhouse gases to our atmosphere if
we could get the same amount of beef
with fewer animals
that could lessen the carbon footprint
of the whole industry
if you're interested in lowering the
environmental footprint of agriculture
geneticists are your friends
but how is it possible to make more
males
in mammals sex is determined by the sex
chromosomes
xx usually means you're female x
y almost always means you're male
but allison told me something pretty
cool
there's actually just a single gene on
the y chromosome
that triggers differentiation down the
male pathway
that's the s r y gene and so what we
were interested in doing is seeing
if we were able to move that gene onto
another chromosome
if we could get male pathway triggered
in an xx individual
allison and her team used crispr to
insert the sry gene
the gene for male development onto
cosmo's
17th chromosome which is a non-sex
chromosome
that means if he has cats that inherit
this sry
gene on the 17th chromosome they might
develop male characteristics even if
they don't inherit
the male y chromosome
and we bring it out here to a 1500 pound
cow
and then we put the egg into embryo
transfer the same way that
is used in human fertility clinics nine
months later we get a calf
the trick is to be as small as i can and
i feel like that dude from lord of the
rings
hi cosmo hi now sadly
cosmo didn't want to be friends
so instead alison let me meet another
newly gene edited calf you have very
pretty eyelashes
one that i could get very close to
here's some lube
they both appreciate this oh but i left
out one detail
this calf is still in utero you're gonna
go in
and you're gonna just gently push she
might give you a little bit of
resistance yeah
you'll feel the opening of her rectum as
you go
through i'm going in oh there's a little
bit of resistance she's good oh yeah
oh yeah so there's manure on my shoe
i want you to gently push down and try
to bounce
or blot below you it feels like there's
like a water balloon but then there's
like a little rock in the water balloon
yeah
is that your baby i feel it
this is crazy and i'm moving around i
know what you're thinking and no
this is not punishment for having scared
the cattle so
next up is ultrasound this is actually
how they perform ultrasounds to check on
the
calves i usually keep my middle finger
on the top of that probe instead of
looking through the belly like on a
human
they look through the intestinal wall by
sticking a probe
up its butt baby baby where are you and
while it might look uncomfortable to us
it doesn't seem to bother the mama cow
very much i'm sorry heifer i have no
idea where i am in you right now
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allison and brett should be able to
determine if a calf is developing as
male or female
after about 70 days you start to see the
vertebral column so the spine of the
calf
yay i saw a little face right now it's
about
the size of a fat cat look at that oh
that'll wash out
yeah it's all good this is not that bad
right
the grand scheme not at all did you
expect worse i did the next step for
allison's research
cosmo needs to grow up and have some
calves of his own
if about half of cosmo's would-be
daughters with two x chromosomes
instead develop as sons the experiment
will have been a success
cosmo looks perfectly normal and healthy
and happy to me he doesn't like me
but i'm not offended by that i don't
take it personally but he looks great
is there anything you worry about an
unintended consequence
with editing in cattle something that
you may not be able to first see in like
two three generations from now
you're always worried did you alter the
genome anywhere else or make a big
deletion
in the case of cosmo he actually got
several copies of
the gene inserted not just the one that
we've designed the construct for so i
mean this is a long way from
ready for prime time and certainly a
long way in my opinion from ready for
doing work in humans
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this raises an important question you
gene edited little marvel do you want to
come be friends with me now
when will crispr be ready for humans
to tackle that we need to understand how
it works today
and how fast it's changing so let's do a
quick crisper
overview now yes
crispr is that drawer in your fridge but
when people talk about crispr they're
usually referring to crispr cast 9.
now this system was discovered in
bacteria as a way for bacteria to defend
themselves against
viruses
here's how it works the dna double helix
is made out of the chemical bases
t g c and a
represented here by colored popsicle
sticks
cast 9 is a protein that acts like
scissors just call me cas9
the molecular scissors and it can be
programmed to cut the dna exactly where
we want
because it also carries with it guide
rna
a one-sided strand of the bases g c
a and u in purple instead of the yellow
t
in the dna but where to cut
it's gonna i got my guide rna scientists
can actually custom build this guide rna
in the lab to match a specific dna
sequence
oh give me a match i'm ready to cut it
and give me a match when the rna that
the cast 9 is carrying lines up
oh snap it's go time
it knows to cut
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once the dna is cut it'll try to repair
itself
and scientists can hack this process by
introducing template dna
that guides what bases are inserted in
the gap
mic drop the ability to edit
genes so how will this affect humanity's
future
so think of it like a pair of scissors
that can go into the dna
i talked to some young artists designers
in their own right
to hear what they think about the
potential for designing
life itself i can do something with a
tree
do a tree dude like maybe people could
have fins or something like i really
don't know
i feel like our scientists are so like
peak technology peak advancements
if they're changing your dna like they
could change
completely how someone will look i do
think that there will be designer babies
in the future most likely
i'ma draw an eyeball right here yeah but
how likely is it
and how soon could we do it safely those
questions are a lot harder to answer
scientists i talk to say there's still a
lot of limitations about what it can and
can't do
crispr normally functions inside a
little teeny tiny bacteria
but when you move it out of bacteria and
into
a human cell now you got to get crisper
in there
in the template dna all of it has to get
into every single cell
it's very inefficient and sometimes
crispr will produce some changes in the
dna
in a lot of cases it's something that
you don't even want
just because we can find the target
doesn't necessarily mean we can make an
accurate change
and making accurate changes that could
lead to disaster
right so scientists like david lu
have been tinkering with the crispr
system to make it more precise
if you think of the original crispr as
it occurs in nature
as a pair of molecular scissors that
cuts the dna double helix
but instead of cutting the dna we
precisely change for example one dna
base pair to a different base pair that
form
of crispr editing is called base editing
if the original crisper is like
molecular scissors you can think of base
editors like pencils
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even though the early scissors version
of crispr is not perfect
it's already being used in clinical
trials to try and disrupt the genetic
mutations that cause diseases like
sickle cell disease or cancer
and even more precise base editors will
be heading into clinical trials soon
so many people may not realize that the
era of
human genome editing that is the era
where we are purposefully making changes
to the dna sequence of human patients
who
are then better off as a result of those
changes
that era is here it's already happened
it's already now
today there are already clinical trials
using crispr
to change genes to treat diseases this
is incredible
now all these clinical trials are using
gene edits that affect only
your body they don't get passed on to
future
offspring that's germline editing that's
a completely different category
this is not designer babies so
are there any human designer babies out
there
yes there are designer babies it's the
work of a scientist
who was looking to genetically modify
the children so that they would have
resistance to hiv
francoise bayless is a bioethicist who
told me about chinese scientist
ha jian kui who in 2018
claimed twin babies were born that he
had genetically edited with crispr
two beautiful little chinese girls came
crying into the world
as healthy as any other babies
then in 2019 a third was born
he was absolutely seeking to push the
boundaries
most of the comments that i have heard
have been critical of the science
and indicating that in large part he
didn't know what he was doing
and so he was roundly criticized for
having done this
in december of 2019 the chinese
government found ha jian kui
guilty of illegal medical practice
and sentenced him to three years in
prison the science
isn't ready at this point in time we
aren't
yet the master of this technology
the technology for germline editing in
humans
isn't there yet the technology is not
precise enough
but pretend for a second it was what
exactly
should we be editing whose decision is
it i spoke to someone who has a really
unique perspective on
all of this in the disability community
we have an expression
nothing about us without us
who is making the decisions who is being
impacted
who will have a voice whether that be
spoken or signed
at the table in those discussions
with the experience of being deaf
it's not merely about not
hearing not hearing noise
it's about how we connect to the world
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in 2019 a russian scientist made
headlines
when he announced that he had recruited
five deaf couples
to participate in a crispr experiment to
quote
correct a gene mutation that causes
deafness
one of the big responses to this
announcement of
this research was why did they choose
deafness let's suppose we have a person
who
is deaf and their family is hereditarily
deaf
all deaf multi-generationally deaf and
signing who do not see
the experience of being deaf as a loss
i think many deaf people are saying hey
our way of life our values
and what we experience what we
contribute
is worthwhile
and to think about throwing that away
without including us in the discussion
is really
unimaginable
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i feel like it just depends genetically
modifying people it depends on what
hands it gets into
to decide that factor if it would turn
for the better or the worse
it's really important now that we invite
everyone to have the opportunity to
participate in this conversation
there are different ways of knowing in
the world and different kinds of
knowledge that have to be respected
come on paint you got this i guess
undesired traits makes you special in a
way
and that's something i don't want my
child to lose i guess
by having all the desired traits
it's a two-way conversation yes there
are things the general public can learn
from the scientific community
but the scientific community can learn
things from the general public
do you think that people should be able
to have that ability to make those
decisions for their children
so if it's changing life-threatening
diseases
i like that idea it'd be pretty helpful
while the ability to edit single gene
mutations is within our grasp
the ability to truly design humans is so
complicated that
we're nowhere close like i don't know
how much your artistic talent comes from
you as a person versus scientists have
barely scratched the surface of even
understanding the genetic basis of
complex traits
like height intelligence or creativity
but the technology is advancing quickly
and its power is so
profound that the time to talk about
this
is right now the project we're talking
about
is ultimately taking over the human
evolutionary story
well we need to think about the human
genome as something that belongs to all
of us
honestly i feel like it's kind of scary
i feel like it would cause like a divide
within like the people that haven't been
genetically
changed or anything the conversation
really is about
the biggest most important question of
all what kind of world do we want to
live in
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to go deeper and meet the brilliant
pioneers behind the crispr gene editing
technology
go watch the documentary feature film
human nature
on nova's website
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you