in this talk we’re going to ask what is heritable human genome editing and when
heritable human genome editing and when
heritable human genome editing and when will it happen and we’ll start off with
will it happen and we’ll start off with
will it happen and we’ll start off with some definitions in the next 15 minutes
some definitions in the next 15 minutes
some definitions in the next 15 minutes or so and then I’ll try and explain what
or so and then I’ll try and explain what
or so and then I’ll try and explain what genome editing is and then I’ll
genome editing is and then I’ll
genome editing is and then I’ll introduce you to some characters
introduce you to some characters
introduce you to some characters throughout this talk
throughout this talk
throughout this talk including the carpenter and then we’ll
including the carpenter and then we’ll
including the carpenter and then we’ll finish with a summary so to those
finish with a summary so to those
finish with a summary so to those definitions well by edit we simply mean
definitions well by edit we simply mean
definitions well by edit we simply mean the standard dictionary definition of
the standard dictionary definition of
the standard dictionary definition of edit where we’re going to make a precise
edit where we’re going to make a precise
edit where we’re going to make a precise controlled change then it can be a very
controlled change then it can be a very
controlled change then it can be a very large change or it can be a very small
large change or it can be a very small
large change or it can be a very small change and what we’re changing is the
change and what we’re changing is the
change and what we’re changing is the genome and the genome is really like an
genome and the genome is really like an
genome and the genome is really like an instruction manual that tells us what we
instruction manual that tells us what we
instruction manual that tells us what we are in a genetic terms and every one or
are in a genetic terms and every one or
are in a genetic terms and every one or most of the trillions of cells in the
most of the trillions of cells in the
most of the trillions of cells in the bodies of each of us contains two
bodies of each of us contains two
bodies of each of us contains two instruction manuals one that we’ve
instruction manuals one that we’ve
instruction manuals one that we’ve inherited from our mother and the other
inherited from our mother and the other
inherited from our mother and the other that we’ve inherited from our father and
that we’ve inherited from our father and
that we’ve inherited from our father and these instruction manuals each one is
these instruction manuals each one is
these instruction manuals each one is huge it contains billions of characters
huge it contains billions of characters
huge it contains billions of characters in fact 3.2 billion characters so if you
in fact 3.2 billion characters so if you
in fact 3.2 billion characters so if you imagine that each one of these
imagine that each one of these
imagine that each one of these characters is a ping pong ball to give
characters is a ping pong ball to give
characters is a ping pong ball to give you an idea of how many characters there
you an idea of how many characters there
you an idea of how many characters there are and in each of your cells if each
are and in each of your cells if each
are and in each of your cells if each one is a ping pong ball there will be
one is a ping pong ball there will be
one is a ping pong ball there will be enough in one cell to fill Wembley
enough in one cell to fill Wembley
enough in one cell to fill Wembley stadium not once or twice or three times
stadium not once or twice or three times
stadium not once or twice or three times or four times or five times but there
or four times or five times but there
or four times or five times but there will be enough ping pong balls to fill
will be enough ping pong balls to fill
will be enough ping pong balls to fill six Wembley stadium as you can see I’m
six Wembley stadium as you can see I’m
six Wembley stadium as you can see I’m talking a lot of balls and if you wanted
talking a lot of balls and if you wanted
talking a lot of balls and if you wanted to target just to make a change to just
to target just to make a change to just
to target just to make a change to just one of those balls among six billion
one of those balls among six billion
one of those balls among six billion that’s a big ask and the history of us
that’s a big ask and the history of us
that’s a big ask and the history of us being able to do that before 1989 looks
being able to do that before 1989 looks
being able to do that before 1989 looks like this nothing we couldn’t do it at
like this nothing we couldn’t do it at
like this nothing we couldn’t do it at all and it wasn’t until the work of
all and it wasn’t until the work of
all and it wasn’t until the work of these three geniuses came together about
these three geniuses came together about
these three geniuses came together about 10 years ago they were awarded the Nobel
10 years ago they were awarded the Nobel
10 years ago they were awarded the Nobel Prize for Physiology or medicine in 2007
Prize for Physiology or medicine in 2007
Prize for Physiology or medicine in 2007 but we could do this for the first time
but we could do this for the first time
but we could do this for the first time in the context of whole animals we did
in the context of whole animals we did
in the context of whole animals we did it mostly for mice and this has been a
it mostly for mice and this has been a
it mostly for mice and this has been a fantastically important method it’s
fantastically important method it’s
fantastically important method it’s really enabled biomedical research but
really enabled biomedical research but
really enabled biomedical research but although what we can now call the
although what we can now call the
although what we can now call the classical method has been extremely
classical method has been extremely
classical method has been extremely important its clunky its slow its
important its clunky its slow its
important its clunky its slow its limited to one target it’s extremely
limited to one target it’s extremely
limited to one target it’s extremely expensive it’s labor intensive
expensive it’s labor intensive
expensive it’s labor intensive there’s restricted expertise not that
there’s restricted expertise not that
there’s restricted expertise not that many people can
many people can
many people can and it has a very variable efficiency
and it has a very variable efficiency
and it has a very variable efficiency and so the search continued for better
and so the search continued for better
and so the search continued for better more improved methods and that search
more improved methods and that search
more improved methods and that search was rewarded in 2005 and 2010 by methods
was rewarded in 2005 and 2010 by methods
was rewarded in 2005 and 2010 by methods that you may have heard of zinc finger
that you may have heard of zinc finger
that you may have heard of zinc finger nucleases ear fens and talons and these
nucleases ear fens and talons and these
nucleases ear fens and talons and these were better but still no cigar and the
were better but still no cigar and the
were better but still no cigar and the search continued and then and then in
search continued and then and then in
search continued and then and then in 2012 and 2013 it was rewarded with Chris
2012 and 2013 it was rewarded with Chris
2012 and 2013 it was rewarded with Chris Bachus 9 with these three publications
Bachus 9 with these three publications
Bachus 9 with these three publications all in science at about that time that
all in science at about that time that
all in science at about that time that reported what Chris Barker’s line does
reported what Chris Barker’s line does
reported what Chris Barker’s line does and what it does is incredibly quick
and what it does is incredibly quick
and what it does is incredibly quick it’s fast it takes weeks not years it
it’s fast it takes weeks not years it
it’s fast it takes weeks not years it you can target many targets at one time
you can target many targets at one time
you can target many targets at one time so you can make multiple edits it’s
so you can make multiple edits it’s
so you can make multiple edits it’s economically it cost hundreds of euros
economically it cost hundreds of euros
economically it cost hundreds of euros not tens of thousands it’s streamlined
not tens of thousands it’s streamlined
not tens of thousands it’s streamlined it’s already widely practiced and it is
it’s already widely practiced and it is
it’s already widely practiced and it is highly efficient you shoot you score so
highly efficient you shoot you score so
highly efficient you shoot you score so although Chris Barker’s line doesn’t do
although Chris Barker’s line doesn’t do
although Chris Barker’s line doesn’t do anything we couldn’t do before it just
anything we couldn’t do before it just
anything we couldn’t do before it just does it so much better that it’s a
does it so much better that it’s a
does it so much better that it’s a game-changer so how does it work well it
game-changer so how does it work well it
game-changer so how does it work well it works in two ways the Chris Park has
works in two ways the Chris Park has
works in two ways the Chris Park has nine first of all does its part which is
nine first of all does its part which is
nine first of all does its part which is to make a break in the genome and then
to make a break in the genome and then
to make a break in the genome and then the cell repairs that break and I’m
the cell repairs that break and I’m
the cell repairs that break and I’m going to talk about each of these one by
going to talk about each of these one by
going to talk about each of these one by one starting with the Chris Barr cast
one starting with the Chris Barr cast
one starting with the Chris Barr cast nine part so this is the Chris Barker’s
nine part so this is the Chris Barker’s
nine part so this is the Chris Barker’s line that’s going to do the genome
line that’s going to do the genome
line that’s going to do the genome editing and in fact it works like a pair
editing and in fact it works like a pair
editing and in fact it works like a pair of tiny molecular scissors and a
of tiny molecular scissors and a
of tiny molecular scissors and a molecular sat-nav and the sat-nav that
molecular sat-nav and the sat-nav that
molecular sat-nav and the sat-nav that you get to program exactly whereabouts
you get to program exactly whereabouts
you get to program exactly whereabouts in the genome you want it to cut tells
in the genome you want it to cut tells
in the genome you want it to cut tells the scissors which you’ve programmed
the scissors which you’ve programmed
the scissors which you’ve programmed where to go and make the cut from the
where to go and make the cut from the
where to go and make the cut from the genome and this is what it looks like
genome and this is what it looks like
genome and this is what it looks like I mean it’s it’s an amazing system
I mean it’s it’s an amazing system
I mean it’s it’s an amazing system really it’s a very simplistic and
really it’s a very simplistic and
really it’s a very simplistic and simplified diagram but in the middle
simplified diagram but in the middle
simplified diagram but in the middle here we have a representation of the
here we have a representation of the
here we have a representation of the genome the genomic DNA and this is a
genome the genomic DNA and this is a
genome the genomic DNA and this is a small part of these six billion
small part of these six billion
small part of these six billion characters per cell and the sat-nav the
characters per cell and the sat-nav the
characters per cell and the sat-nav the molecular sat-nav is actually looks
molecular sat-nav is actually looks
molecular sat-nav is actually looks really boring really prosaic and it’s
really boring really prosaic and it’s
really boring really prosaic and it’s this bit here it’s about a hundred and
this bit here it’s about a hundred and
this bit here it’s about a hundred and ten characters long it’s called an RNA
ten characters long it’s called an RNA
ten characters long it’s called an RNA molecule or a guide RNA molecule and
molecule or a guide RNA molecule and
molecule or a guide RNA molecule and although it looks boring it’s amazing
although it looks boring it’s amazing
although it looks boring it’s amazing because what it can do is interact with
because what it can do is interact with
because what it can do is interact with two things one part of it can interact
two things one part of it can interact
two things one part of it can interact with the pink blobby thing here
with the pink blobby thing here
with the pink blobby thing here are actually the molecular scissors they
are actually the molecular scissors they
are actually the molecular scissors they do the cutting and the other part twenty
do the cutting and the other part twenty
do the cutting and the other part twenty characters worth can zip up with twenty
characters worth can zip up with twenty
characters worth can zip up with twenty characters is specifically a twenty
characters is specifically a twenty
characters is specifically a twenty character to stretch within that six
character to stretch within that six
character to stretch within that six point four billion nucleotides of genome
point four billion nucleotides of genome
point four billion nucleotides of genome sequence and that twenty characters is
sequence and that twenty characters is
sequence and that twenty characters is enough to endow exquisite specificity to
enough to endow exquisite specificity to
enough to endow exquisite specificity to the whole system so then once that’s
the whole system so then once that’s
the whole system so then once that’s happened I’ve changed metaphors now so
happened I’ve changed metaphors now so
happened I’ve changed metaphors now so now we’re moving from an instruction
now we’re moving from an instruction
now we’re moving from an instruction manual to imagine the genome is like a
manual to imagine the genome is like a
manual to imagine the genome is like a piece of string and we’ve cut the piece
piece of string and we’ve cut the piece
piece of string and we’ve cut the piece of string exactly where we want with our
of string exactly where we want with our
of string exactly where we want with our crisp our cast nine and now the cell has
crisp our cast nine and now the cell has
crisp our cast nine and now the cell has to repair that cut because these
to repair that cut because these
to repair that cut because these double-stranded breaks as they’re called
double-stranded breaks as they’re called
double-stranded breaks as they’re called are bad news for cells they sometimes
are bad news for cells they sometimes
are bad news for cells they sometimes occur naturally and if they’re not
occur naturally and if they’re not
occur naturally and if they’re not rapidly repaired the cell can die and
rapidly repaired the cell can die and
rapidly repaired the cell can die and indeed it can be even worse the entire
indeed it can be even worse the entire
indeed it can be even worse the entire organism can die this is one way that
organism can die this is one way that
organism can die this is one way that cancer is initiated so the cell quickly
cancer is initiated so the cell quickly
cancer is initiated so the cell quickly has to repair this and the way it does
has to repair this and the way it does
has to repair this and the way it does this so made out we’ve made our break
this so made out we’ve made our break
this so made out we’ve made our break here with the CRISPR cast line in a
here with the CRISPR cast line in a
here with the CRISPR cast line in a specified place that now targets the
specified place that now targets the
specified place that now targets the cellular repair machinery all of this
cellular repair machinery all of this
cellular repair machinery all of this happens inside a cell each of your cells
happens inside a cell each of your cells
happens inside a cell each of your cells has this machinery and what it does is
has this machinery and what it does is
has this machinery and what it does is it kind of acts like it uses the good
it kind of acts like it uses the good
it kind of acts like it uses the good instruction manual naturally to repair
instruction manual naturally to repair
instruction manual naturally to repair the bad instruction manual to which the
the bad instruction manual to which the
the bad instruction manual to which the damage has occurred but what we’ve done
damage has occurred but what we’ve done
damage has occurred but what we’ve done is we’ve targeted the particular damage
is we’ve targeted the particular damage
is we’ve targeted the particular damage the cut in the instruction manual or cut
the cut in the instruction manual or cut
the cut in the instruction manual or cut in the genome and now we can flood the
in the genome and now we can flood the
in the genome and now we can flood the whole system the cell with the
whole system the cell with the
whole system the cell with the information to repair just that part and
information to repair just that part and
information to repair just that part and we can get to write the page or the
we can get to write the page or the
we can get to write the page or the sentences we can insert bits or we can
sentences we can insert bits or we can
sentences we can insert bits or we can remove them and it looks a little bit
remove them and it looks a little bit
remove them and it looks a little bit like if we homed in on this it looks to
like if we homed in on this it looks to
like if we homed in on this it looks to me a little bit like a bridge so we’ve
me a little bit like a bridge so we’ve
me a little bit like a bridge so we’ve got our extra piece of genome here just
got our extra piece of genome here just
got our extra piece of genome here just a relatively small piece and it looks
a relatively small piece and it looks
a relatively small piece and it looks like a bridge where the left foot of the
like a bridge where the left foot of the
like a bridge where the left foot of the bridge perfectly matches the left-hand
bridge perfectly matches the left-hand
bridge perfectly matches the left-hand side of the brake made by Chris Barker
side of the brake made by Chris Barker
side of the brake made by Chris Barker slime and the right side foot of the
slime and the right side foot of the
slime and the right side foot of the bridge matches perfectly the right side
bridge matches perfectly the right side
bridge matches perfectly the right side of the brake but what’s in the middle
of the brake but what’s in the middle
of the brake but what’s in the middle the span of the bridge you get to decide
the span of the bridge you get to decide
the span of the bridge you get to decide what to put in so you can make a very
what to put in so you can make a very
what to put in so you can make a very short span in fact it can correspond to
short span in fact it can correspond to
short span in fact it can correspond to a deletion of the DNA or a very long
a deletion of the DNA or a very long
a deletion of the DNA or a very long insertion you can put fouls
insertion you can put fouls
insertion you can put fouls of characters in if you want to so all
of characters in if you want to so all
of characters in if you want to so all of this really reminds me now of the
of this really reminds me now of the
of this really reminds me now of the carpenter it’s as if we’ve given the
carpenter it’s as if we’ve given the
carpenter it’s as if we’ve given the carpenter a molecular carpenter some
carpenter a molecular carpenter some
carpenter a molecular carpenter some amazing new tools and of course like all
amazing new tools and of course like all
amazing new tools and of course like all carpenters he or she has a vision for
carpenters he or she has a vision for
carpenters he or she has a vision for what they want to make with these tools
what they want to make with these tools
what they want to make with these tools and using their experience and expertise
and using their experience and expertise
and using their experience and expertise they apply the tools to realize the
they apply the tools to realize the
they apply the tools to realize the vision using the process so the vision
vision using the process so the vision
vision using the process so the vision that they have in the context of Chris
that they have in the context of Chris
that they have in the context of Chris bark has nine is likely to be clinical
bark has nine is likely to be clinical
bark has nine is likely to be clinical so most people are thinking that we can
so most people are thinking that we can
so most people are thinking that we can use this in the treatment or prevention
use this in the treatment or prevention
use this in the treatment or prevention of heritable or disease that’s genetic
of heritable or disease that’s genetic
of heritable or disease that’s genetic with a genetic component and to
with a genetic component and to
with a genetic component and to illustrate what that might be I’d like
illustrate what that might be I’d like
illustrate what that might be I’d like to introduce you to Chubb Shaw chop Shaw
to introduce you to Chubb Shaw chop Shaw
to introduce you to Chubb Shaw chop Shaw was born on the 22nd of April 2013 by
was born on the 22nd of April 2013 by
was born on the 22nd of April 2013 by the ages by the time he’s aged 17 he’ll
the ages by the time he’s aged 17 he’ll
the ages by the time he’s aged 17 he’ll become a multi-billionaire and at 28
become a multi-billionaire and at 28
become a multi-billionaire and at 28 he’ll be the founder of chop Shawn lunar
he’ll be the founder of chop Shawn lunar
he’ll be the founder of chop Shawn lunar mining Inc but when he’s 34 he’ll be
mining Inc but when he’s 34 he’ll be
mining Inc but when he’s 34 he’ll be diagnosed with a heritable terminal
diagnosed with a heritable terminal
diagnosed with a heritable terminal neurodegenerative disease what hope
neurodegenerative disease what hope
neurodegenerative disease what hope might there be for trouble and people
might there be for trouble and people
might there be for trouble and people liked rupture in 2047 well we might
liked rupture in 2047 well we might
liked rupture in 2047 well we might combine several different technologies
combine several different technologies
combine several different technologies including genome editing like this
including genome editing like this
including genome editing like this rubbish all might go to his hospital or
rubbish all might go to his hospital or
rubbish all might go to his hospital or clinic and give a simple cheek cell swab
clinic and give a simple cheek cell swab
clinic and give a simple cheek cell swab to the practitioner to the clinician to
to the practitioner to the clinician to
to the practitioner to the clinician to the doctor and they will take them away
the doctor and they will take them away
the doctor and they will take them away and they will use something called
and they will use something called
and they will use something called induced pluripotent C which we can now
induced pluripotent C which we can now
induced pluripotent C which we can now do in humans as well as it was
do in humans as well as it was
do in humans as well as it was discovered in mice initially and what
discovered in mice initially and what
discovered in mice initially and what that happen cells and make them like
that happen cells and make them like
that happen cells and make them like embryo cells they’re not embryos but
embryo cells they’re not embryos but
embryo cells they’re not embryos but they’re like embryo cells and we can
they’re like embryo cells and we can
they’re like embryo cells and we can cause these cells to proliferate we can
cause these cells to proliferate we can
cause these cells to proliferate we can grow them in the dish and that gives us
grow them in the dish and that gives us
grow them in the dish and that gives us an opportunity to do editing so we could
an opportunity to do editing so we could
an opportunity to do editing so we could go in now we can add all of our other
go in now we can add all of our other
go in now we can add all of our other CRISPR cache line components and we can
CRISPR cache line components and we can
CRISPR cache line components and we can change the affected gene that
change the affected gene that
change the affected gene that predisposes to truck shores condition
predisposes to truck shores condition
predisposes to truck shores condition and now we can take those cells because
and now we can take those cells because
and now we can take those cells because their embryo like cells we can ask them
their embryo like cells we can ask them
their embryo like cells we can ask them to become neurons so we can ask them
to become neurons so we can ask them
to become neurons so we can ask them this is called directed differentiation
this is called directed differentiation
this is called directed differentiation to become like neurons and because it’s
to become like neurons and because it’s
to become like neurons and because it’s all really derived from truck Shaw in a
all really derived from truck Shaw in a
all really derived from truck Shaw in a way we can now transplant them back into
way we can now transplant them back into
way we can now transplant them back into truck Shaw so that rupture is cured her
truck Shaw so that rupture is cured her
truck Shaw so that rupture is cured her so off he goes and of course he’s very
so off he goes and of course he’s very
so off he goes and of course he’s very rich he’s a multi-billionaire
rich he’s a multi-billionaire
rich he’s a multi-billionaire all this stuff so that so the girls love
all this stuff so that so the girls love
all this stuff so that so the girls love him but he finds the love of his life he
him but he finds the love of his life he
him but he finds the love of his life he meets Mrs T and they decide but they
meets Mrs T and they decide but they
meets Mrs T and they decide but they want to have they want to start a family
want to have they want to start a family
want to have they want to start a family they want to have children the thing
they want to have children the thing
they want to have children the thing about having children of course is that
about having children of course is that
about having children of course is that truck Shaw’s gene that predisposed his
truck Shaw’s gene that predisposed his
truck Shaw’s gene that predisposed his neuro degeneration might be inherited by
neuro degeneration might be inherited by
neuro degeneration might be inherited by trouble jr. because we’ve only fixed
trouble jr. because we’ve only fixed
trouble jr. because we’ve only fixed ruptures neurons so what hope might
ruptures neurons so what hope might
ruptures neurons so what hope might there be for trouble jr. in the future
there be for trouble jr. in the future
there be for trouble jr. in the future and this is where we come to heritable
and this is where we come to heritable
and this is where we come to heritable human genome editing by Chris Park as
human genome editing by Chris Park as
human genome editing by Chris Park as 9so inheritable genome editing what
9so inheritable genome editing what
9so inheritable genome editing what we’re talking about is a change and edit
we’re talking about is a change and edit
we’re talking about is a change and edit that we make that can be transmitted to
that we make that can be transmitted to
that we make that can be transmitted to future generations and there are two
future generations and there are two
future generations and there are two hypothetical strategies in humans that
hypothetical strategies in humans that
hypothetical strategies in humans that we might do this so we’re putting the
we might do this so we’re putting the
we might do this so we’re putting the pieces together in mice and model
pieces together in mice and model
pieces together in mice and model systems but so far everything I’m going
systems but so far everything I’m going
systems but so far everything I’m going to say from now on is really
to say from now on is really
to say from now on is really hypothetical we think that it’s in reach
hypothetical we think that it’s in reach
hypothetical we think that it’s in reach and it’s foreseeable but it’s actually
and it’s foreseeable but it’s actually
and it’s foreseeable but it’s actually hypothetical in humans but what we think
hypothetical in humans but what we think
hypothetical in humans but what we think we’ll be able to do is we’ll be able to
we’ll be able to do is we’ll be able to
we’ll be able to do is we’ll be able to either edit in the embryo or edit in
either edit in the embryo or edit in
either edit in the embryo or edit in gametes or sperm and the egg and I’m
gametes or sperm and the egg and I’m
gametes or sperm and the egg and I’m going to talk about these one by one
going to talk about these one by one
going to talk about these one by one starting with the embryo so embryos of
starting with the embryo so embryos of
starting with the embryo so embryos of the type that we’re talking about are
the type that we’re talking about are
the type that we’re talking about are one cell embryos we all owe our origins
one cell embryos we all owe our origins
one cell embryos we all owe our origins to the one cell embryo stage at some
to the one cell embryo stage at some
to the one cell embryo stage at some point okay this is actually a mouse one
point okay this is actually a mouse one
point okay this is actually a mouse one cell embryo but humanum one cell embryos
cell embryo but humanum one cell embryos
cell embryo but humanum one cell embryos look very similar and you can see here
look very similar and you can see here
look very similar and you can see here the maternal and mother derive and the
the maternal and mother derive and the
the maternal and mother derive and the father’s instruction manuals before they
father’s instruction manuals before they
father’s instruction manuals before they come together and we can inject into
come together and we can inject into
come together and we can inject into this one so using a very gentle
this one so using a very gentle
this one so using a very gentle injection protocol the Chris spark has
injection protocol the Chris spark has
injection protocol the Chris spark has nine components that then can fix the
nine components that then can fix the
nine components that then can fix the gene so that now the embryo can develop
gene so that now the embryo can develop
gene so that now the embryo can develop and we can use standard assisted
and we can use standard assisted
and we can use standard assisted reproductive technologies with a which
reproductive technologies with a which
reproductive technologies with a which are current today in many fertility
are current today in many fertility
are current today in many fertility clinics to transfer the embryo into mrs.
clinics to transfer the embryo into mrs.
clinics to transfer the embryo into mrs. T she can carry the pregnancy and so
T she can carry the pregnancy and so
T she can carry the pregnancy and so when rubbish or jr. is born all of his
when rubbish or jr. is born all of his
when rubbish or jr. is born all of his cells now contain that edit so he will
cells now contain that edit so he will
cells now contain that edit so he will not be predisposed to the
not be predisposed to the
not be predisposed to the neurodegenerative disease that his
neurodegenerative disease that his
neurodegenerative disease that his father had in the same way and there are
father had in the same way and there are
father had in the same way and there are in fact many single gene conditions that
in fact many single gene conditions that
in fact many single gene conditions that this kind of approach would would apply
this kind of approach would would apply
this kind of approach would would apply to and although they are so there are
to and although they are so there are
to and although they are so there are probably about 6,000 probably more than
probably about 6,000 probably more than
probably about 6,000 probably more than 6,000 that are known and although each
6,000 that are known and although each
6,000 that are known and although each one of these is individually quite rare
one of these is individually quite rare
one of these is individually quite rare together they really add up to something
together they really add up to something
together they really add up to something and in the UK where I’m from there are
and in the UK where I’m from there are
and in the UK where I’m from there are probably a million people who are
probably a million people who are
probably a million people who are affected in this way so it’s really very
affected in this way so it’s really very
affected in this way so it’s really very important but actually most disease has
important but actually most disease has
important but actually most disease has a genetic component from multiple
a genetic component from multiple
a genetic component from multiple different genes and this includes all of
different genes and this includes all of
different genes and this includes all of our many of them all of our old
our many of them all of our old
our many of them all of our old favorites cardiovascular disease
favorites cardiovascular disease
favorites cardiovascular disease diabetes obesity cancer
diabetes obesity cancer
diabetes obesity cancer irritable bowel disease multiple squares
irritable bowel disease multiple squares
irritable bowel disease multiple squares a very long list which affects many many
a very long list which affects many many
a very long list which affects many many millions of people so the thing about
millions of people so the thing about
millions of people so the thing about these diseases is that although they are
these diseases is that although they are
these diseases is that although they are of course massively important because
of course massively important because
of course massively important because they have a different contribution from
they have a different contribution from
they have a different contribution from the environment and from multiple
the environment and from multiple
the environment and from multiple different genes we don’t understand them
different genes we don’t understand them
different genes we don’t understand them we don’t understand the genetics and so
we don’t understand the genetics and so
we don’t understand the genetics and so they’re often overlooked but that’s
they’re often overlooked but that’s
they’re often overlooked but that’s going to change and it’s going to change
going to change and it’s going to change
going to change and it’s going to change with one particular technology in
with one particular technology in
with one particular technology in particular and that is whole genome
particular and that is whole genome
particular and that is whole genome sequencing so the first human whole
sequencing so the first human whole
sequencing so the first human whole genome sequence was published in 2001 at
genome sequence was published in 2001 at
genome sequence was published in 2001 at a cost of approximately a hundred
a cost of approximately a hundred
a cost of approximately a hundred million dollars u.s. dollars and this
million dollars u.s. dollars and this
million dollars u.s. dollars and this chart here you can’t see the details but
chart here you can’t see the details but
chart here you can’t see the details but it doesn’t really matter
it doesn’t really matter
it doesn’t really matter shows how the cost of sequencing a whole
shows how the cost of sequencing a whole
shows how the cost of sequencing a whole genome from humans has decreased in the
genome from humans has decreased in the
genome from humans has decreased in the years since 2001 now if this cost had
years since 2001 now if this cost had
years since 2001 now if this cost had decreased according to Moore’s law so so
decreased according to Moore’s law so so
decreased according to Moore’s law so so Gordon Moore was was one of the
Gordon Moore was was one of the
Gordon Moore was was one of the cofounders of Intel and he came up in a
cofounders of Intel and he came up in a
cofounders of Intel and he came up in a 1965 paper with the idea that the number
1965 paper with the idea that the number
1965 paper with the idea that the number of he predicted that the number of
of he predicted that the number of
of he predicted that the number of transistors that you could fit on a on
transistors that you could fit on a on
transistors that you could fit on a on an integrated circuit would double more
an integrated circuit would double more
an integrated circuit would double more or less every year the computer power
or less every year the computer power
or less every year the computer power would double every every year and there
would double every every year and there
would double every every year and there have been different iterations of that
have been different iterations of that
have been different iterations of that idea but basically he’s been right but
idea but basically he’s been right but
idea but basically he’s been right but if we followed with genome sequencing
if we followed with genome sequencing
if we followed with genome sequencing this trajectory the cost today would be
this trajectory the cost today would be
this trajectory the cost today would be about just under a million u.s. dollars
about just under a million u.s. dollars
about just under a million u.s. dollars per genome per human genome sequence in
per genome per human genome sequence in
per genome per human genome sequence in fact something different has happened if
fact something different has happened if
fact something different has happened if you look at this just graph this graph
you look at this just graph this graph
you look at this just graph this graph here which plots logarithmically the
here which plots logarithmically the
here which plots logarithmically the last ten years the cost has been coming
last ten years the cost has been coming
last ten years the cost has been coming down five times per year fivefold per
down five times per year fivefold per
down five times per year fivefold per year every year it gets a fifth of the
year every year it gets a fifth of the
year every year it gets a fifth of the cost so that means if we project forward
cost so that means if we project forward
cost so that means if we project forward in five years time it will cost just 25
in five years time it will cost just 25
in five years time it will cost just 25 cents to sequence your genome so what
cents to sequence your genome so what
cents to sequence your genome so what you’ll be able to do
you’ll be able to do
you’ll be able to do is you’ll be able to go to your local
is you’ll be able to go to your local
is you’ll be able to go to your local supermarket too the whole genome
supermarket too the whole genome
supermarket too the whole genome sequencing counter give a swab from your
sequencing counter give a swab from your
sequencing counter give a swab from your cheek cell they’ll take it off in a
cheek cell they’ll take it off in a
cheek cell they’ll take it off in a drone and it will be sent to a
drone and it will be sent to a
drone and it will be sent to a sequencing center and then they will
sequencing center and then they will
sequencing center and then they will produce the information it’ll go up to
produce the information it’ll go up to
produce the information it’ll go up to the cloud and the cloud and they’ll send
the cloud and the cloud and they’ll send
the cloud and the cloud and they’ll send it to your healthcare provider or doctor
it to your healthcare provider or doctor
it to your healthcare provider or doctor or insurer or whoever fantastic but what
or insurer or whoever fantastic but what
or insurer or whoever fantastic but what does this mean well I think what it’s
does this mean well I think what it’s
does this mean well I think what it’s going to mean is that we’re going to
going to mean is that we’re going to
going to mean is that we’re going to identify new disease genes because these
identify new disease genes because these
identify new disease genes because these sequences at 25 cents each we’ll be able
sequences at 25 cents each we’ll be able
sequences at 25 cents each we’ll be able to sequence people with from addis ababa
to sequence people with from addis ababa
to sequence people with from addis ababa or a delayed or thessaloniki or wherever
or a delayed or thessaloniki or wherever
or a delayed or thessaloniki or wherever and we’ll be able to say well if you’ve
and we’ll be able to say well if you’ve
and we’ll be able to say well if you’ve got that character that character that
got that character that character that
got that character that character that page there that paragraph there that
page there that paragraph there that
page there that paragraph there that paragraph there then you’ve got a 78%
paragraph there then you’ve got a 78%
paragraph there then you’ve got a 78% chance of having hypertension by the
chance of having hypertension by the
chance of having hypertension by the time you’re 62 and so then people are
time you’re 62 and so then people are
time you’re 62 and so then people are going to say well you know that this is
going to say well you know that this is
going to say well you know that this is and they’re gonna we’re going to find
and they’re gonna we’re going to find
and they’re gonna we’re going to find out these associations possibly for all
out these associations possibly for all
out these associations possibly for all diseases and indeed health if you’ve got
diseases and indeed health if you’ve got
diseases and indeed health if you’ve got these things then you’re more likely to
these things then you’re more likely to
these things then you’re more likely to be healthy so the other corollary of
be healthy so the other corollary of
be healthy so the other corollary of this of course is that every embryo is
this of course is that every embryo is
this of course is that every embryo is going to have some genes or some
going to have some genes or some
going to have some genes or some sequences that predispose to bad things
sequences that predispose to bad things
sequences that predispose to bad things happening perhaps many years in the
happening perhaps many years in the
happening perhaps many years in the future so what hope will there be for
future so what hope will there be for
future so what hope will there be for editing to fix these multiple changes
editing to fix these multiple changes
editing to fix these multiple changes and we return here to our two methods we
and we return here to our two methods we
and we return here to our two methods we could edit in the embryo but this is
could edit in the embryo but this is
could edit in the embryo but this is unlikely because the white window of
unlikely because the white window of
unlikely because the white window of opportunity is quite short to do
opportunity is quite short to do
opportunity is quite short to do multiple editing and to confirm what’s
multiple editing and to confirm what’s
multiple editing and to confirm what’s happening and there’s a risk that we
happening and there’s a risk that we
happening and there’s a risk that we might end up with scrambled eggs so it’s
might end up with scrambled eggs so it’s
might end up with scrambled eggs so it’s more likely that we’ll use the second
more likely that we’ll use the second
more likely that we’ll use the second method here gamete editing where edit
method here gamete editing where edit
method here gamete editing where edit sperm and eggs and very recently we’ve
sperm and eggs and very recently we’ve
sperm and eggs and very recently we’ve started to develop the technology to do
started to develop the technology to do
started to develop the technology to do this in mice so what it’ll happen in the
this in mice so what it’ll happen in the
this in mice so what it’ll happen in the future with mr. t for example is that
future with mr. t for example is that
future with mr. t for example is that mr. t will go along and generate IPS
mr. t will go along and generate IPS
mr. t will go along and generate IPS cells from his cheek cells but instead
cells from his cheek cells but instead
cells from his cheek cells but instead of turning these into neurons which we
of turning these into neurons which we
of turning these into neurons which we did before after we’ve done the editing
did before after we’ve done the editing
did before after we’ve done the editing we can do editing check it’s okay more
we can do editing check it’s okay more
we can do editing check it’s okay more editing check it’s okay of the IPS cells
editing check it’s okay of the IPS cells
editing check it’s okay of the IPS cells in the dish then we can turn them into
in the dish then we can turn them into
in the dish then we can turn them into sperm cells and using standard
sperm cells and using standard
sperm cells and using standard reproductive technology inject these
reproductive technology inject these
reproductive technology inject these into eggs then mrs. T becomes pregnant
into eggs then mrs. T becomes pregnant
into eggs then mrs. T becomes pregnant so that now chop saw jr. has multiple
so that now chop saw jr. has multiple
so that now chop saw jr. has multiple genes edited from the paternal germline
genes edited from the paternal germline
genes edited from the paternal germline similarly with Mrs T mrs. T might have
similarly with Mrs T mrs. T might have
similarly with Mrs T mrs. T might have some so-called problem genes and we
some so-called problem genes and we
some so-called problem genes and we can address those too we could do
can address those too we could do
can address those too we could do similar kind of edits except this time
similar kind of edits except this time
similar kind of edits except this time we can ask the IPS cells derived from
we can ask the IPS cells derived from
we can ask the IPS cells derived from Mrs T to become eggs so now we can match
Mrs T to become eggs so now we can match
Mrs T to become eggs so now we can match them both together and we can produce
them both together and we can produce
them both together and we can produce truck sure that’s got edits on both
truck sure that’s got edits on both
truck sure that’s got edits on both sides multiple edits so now the
sides multiple edits so now the
sides multiple edits so now the carpenter is really given a fantastic
carpenter is really given a fantastic
carpenter is really given a fantastic toolkit with which to realize his vision
toolkit with which to realize his vision
toolkit with which to realize his vision the problem is that his vision and the
the problem is that his vision and the
the problem is that his vision and the vision of other people might not be
vision of other people might not be
vision of other people might not be quite the same as troubles vision trap
quite the same as troubles vision trap
quite the same as troubles vision trap Shaw might not be satisfied with
Shaw might not be satisfied with
Shaw might not be satisfied with repairing disease predisposing genes he
repairing disease predisposing genes he
repairing disease predisposing genes he might want to have a family of you know
might want to have a family of you know
might want to have a family of you know Lara Croft’s and Jason Bourne’s right so
Lara Croft’s and Jason Bourne’s right so
Lara Croft’s and Jason Bourne’s right so then that brings the idea of enhancement
then that brings the idea of enhancement
then that brings the idea of enhancement using genome editing for enhancement and
using genome editing for enhancement and
using genome editing for enhancement and this is where we’re altering traits
this is where we’re altering traits
this is where we’re altering traits genetically that are not necessarily
genetically that are not necessarily
genetically that are not necessarily directly related to disease things like
directly related to disease things like
directly related to disease things like I’ve listed some of them it’s quite good
I’ve listed some of them it’s quite good
I’ve listed some of them it’s quite good fun to just think of the lists strength
fun to just think of the lists strength
fun to just think of the lists strength endurance IQ for example this is a kind
endurance IQ for example this is a kind
endurance IQ for example this is a kind of transhumanism light and it kind of
of transhumanism light and it kind of
of transhumanism light and it kind of introduces the notion of designer babies
introduces the notion of designer babies
introduces the notion of designer babies but there’s also transhumanism not so
but there’s also transhumanism not so
but there’s also transhumanism not so light which is much more fantastic where
light which is much more fantastic where
light which is much more fantastic where we’re thinking about adding traits to
we’re thinking about adding traits to
we’re thinking about adding traits to humans right you want your kid to be
humans right you want your kid to be
humans right you want your kid to be able to fly to school in the morning
able to fly to school in the morning
able to fly to school in the morning madam no problem well give him or her
madam no problem well give him or her
madam no problem well give him or her wings but there’s a problem with this ok
wings but there’s a problem with this ok
wings but there’s a problem with this ok there are several problems with it but
there are several problems with it but
there are several problems with it but the one problem that I want to focus on
the one problem that I want to focus on
the one problem that I want to focus on is that we’re forgetting the process so
is that we’re forgetting the process so
is that we’re forgetting the process so the carpenter is in his or her workshop
the carpenter is in his or her workshop
the carpenter is in his or her workshop with the tools which we’ve given him he
with the tools which we’ve given him he
with the tools which we’ve given him he or she has the vision but we’re
or she has the vision but we’re
or she has the vision but we’re forgetting the process by which he or
forgetting the process by which he or
forgetting the process by which he or she applies those tools to realize the
she applies those tools to realize the
she applies those tools to realize the vision and this is the same problem that
vision and this is the same problem that
vision and this is the same problem that beset Charles Babbage Charles Babbage
beset Charles Babbage Charles Babbage
beset Charles Babbage Charles Babbage was born in 1791 and he’s credited with
was born in 1791 and he’s credited with
was born in 1791 and he’s credited with being one of the pioneers of the modern
being one of the pioneers of the modern
being one of the pioneers of the modern computer but he was asked his computer
computer but he was asked his computer
computer but he was asked his computer his calculator was called a difference
his calculator was called a difference
his calculator was called a difference engine and he was asked more than one
engine and he was asked more than one
engine and he was asked more than one time in his lifetime mr. Babbage if I
time in his lifetime mr. Babbage if I
time in his lifetime mr. Babbage if I put the wrong values into your
put the wrong values into your
put the wrong values into your calculating machine will it still give
calculating machine will it still give
calculating machine will it still give me the right answer now we can laugh at
me the right answer now we can laugh at
me the right answer now we can laugh at this question but it’s the same mistake
this question but it’s the same mistake
this question but it’s the same mistake that many people are making
that many people are making
that many people are making today I think because we may not know
today I think because we may not know
today I think because we may not know the correct sequences or the correct
the correct sequences or the correct
the correct sequences or the correct values we may not know the correct
values we may not know the correct
values we may not know the correct sequences to edit we probably do for
sequences to edit we probably do for
sequences to edit we probably do for some single gene conditions but for the
some single gene conditions but for the
some single gene conditions but for the multiple the complex gene conditions of
multiple the complex gene conditions of
multiple the complex gene conditions of the complex traits we almost certainly
the complex traits we almost certainly
the complex traits we almost certainly do not know them but until we do know
do not know them but until we do know
do not know them but until we do know them until we know the correct sequence
them until we know the correct sequence
them until we know the correct sequence is to edit we cannot reliably get the
is to edit we cannot reliably get the
is to edit we cannot reliably get the right answer
right answer
right answer and so if at the end of this talk I
and so if at the end of this talk I
and so if at the end of this talk I return to the questions that we asked at
return to the questions that we asked at
return to the questions that we asked at the very beginning what is human
the very beginning what is human
the very beginning what is human heritable genome editing and when will
heritable genome editing and when will
heritable genome editing and when will it happen I think that what we can say
it happen I think that what we can say
it happen I think that what we can say is that it will probably be involved
is that it will probably be involved
is that it will probably be involved Chris Bachus 9 so that heritable human
Chris Bachus 9 so that heritable human
Chris Bachus 9 so that heritable human genome editing is the use of the CRISPR
genome editing is the use of the CRISPR
genome editing is the use of the CRISPR cast line system to make prescribed
cast line system to make prescribed
cast line system to make prescribed changes in gametes and sperm or egg or
changes in gametes and sperm or egg or
changes in gametes and sperm or egg or early embryos and that then the when
early embryos and that then the when
early embryos and that then the when there is some tension here to accelerate
there is some tension here to accelerate
there is some tension here to accelerate the development there is there will be
the development there is there will be
the development there is there will be rapid advances in sequencing technology
rapid advances in sequencing technology
rapid advances in sequencing technology and they will drive demand for sequences
and they will drive demand for sequences
and they will drive demand for sequences for the for editing but on the other
for the for editing but on the other
for the for editing but on the other hand technical legislative political and
hand technical legislative political and
hand technical legislative political and social considerations may push human
social considerations may push human
social considerations may push human genome editing years perhaps even
genome editing years perhaps even
genome editing years perhaps even decades into the future thank you very
decades into the future thank you very
decades into the future thank you very much
”
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