what I’d like you to do is imagine what it was like when you were very very
it was like when you were very very
it was like when you were very very young not one or two years old but
young not one or two years old but
young not one or two years old but basically nine months before you were
basically nine months before you were
basically nine months before you were born
born
born what happens is you started off as a
what happens is you started off as a
what happens is you started off as a single cell all your genetic material
single cell all your genetic material
single cell all your genetic material came from mum and dad they passed on two
came from mum and dad they passed on two
came from mum and dad they passed on two sets of chromosomes so we have up here a
sets of chromosomes so we have up here a
sets of chromosomes so we have up here a picture of the human karyotypes female
picture of the human karyotypes female
picture of the human karyotypes female on the Left male on the right so the
on the Left male on the right so the
on the Left male on the right so the only difference between these are all
only difference between these are all
only difference between these are all circle stay on the bottom the females
circle stay on the bottom the females
circle stay on the bottom the females have two X chromosomes males have One X
have two X chromosomes males have One X
have two X chromosomes males have One X chromosome and a white chromosome now
chromosome and a white chromosome now
chromosome and a white chromosome now DNA superficial it’s incredibly boring
DNA superficial it’s incredibly boring
DNA superficial it’s incredibly boring it’s just a long molecule with four
it’s just a long molecule with four
it’s just a long molecule with four different letters ACGT
different letters ACGT
different letters ACGT and it’s the order of these ACGT that
and it’s the order of these ACGT that
and it’s the order of these ACGT that carries all our genetic code from a
carries all our genetic code from a
carries all our genetic code from a single cell you’ve obviously grown a
single cell you’ve obviously grown a
single cell you’ve obviously grown a little bit
little bit
little bit you’ve got kidneys liver brain skin all
you’ve got kidneys liver brain skin all
you’ve got kidneys liver brain skin all sorts of different cells they all have
sorts of different cells they all have
sorts of different cells they all have the same genetic makeup different genes
the same genetic makeup different genes
the same genetic makeup different genes are expressed in different tissues some
are expressed in different tissues some
are expressed in different tissues some are switched on some are switched off
are switched on some are switched off
are switched on some are switched off I’ve been fascinated by how genes work
I’ve been fascinated by how genes work
I’ve been fascinated by how genes work because when you can work out how a gene
because when you can work out how a gene
because when you can work out how a gene is working you can start coming up with
is working you can start coming up with
is working you can start coming up with potential therapies to try and treat
potential therapies to try and treat
potential therapies to try and treat them now we have 23,000 different genes
them now we have 23,000 different genes
them now we have 23,000 different genes sounds impressive we have three billion
sounds impressive we have three billion
sounds impressive we have three billion letters ACGT that make up each set of
letters ACGT that make up each set of
letters ACGT that make up each set of chromosomes so that sounds impressive
chromosomes so that sounds impressive
chromosomes so that sounds impressive but let’s put up the context we’re
but let’s put up the context we’re
but let’s put up the context we’re outgunned by the water flea we have
outgunned by the water flea we have
outgunned by the water flea we have 23,000 genes the water flea Daphnia has
23,000 genes the water flea Daphnia has
23,000 genes the water flea Daphnia has 31,000 genes there are plants out there
31,000 genes there are plants out there
31,000 genes there are plants out there that have 50 times the amount of DNA in
that have 50 times the amount of DNA in
that have 50 times the amount of DNA in their cells and we do so obvious it’s
their cells and we do so obvious it’s
their cells and we do so obvious it’s not how much DNA you’ve got or how many
not how much DNA you’ve got or how many
not how much DNA you’ve got or how many genes but how you use them so if we go
genes but how you use them so if we go
genes but how you use them so if we go off to our picture of a little segment
off to our picture of a little segment
off to our picture of a little segment of DNA which carries the genetic
of DNA which carries the genetic
of DNA which carries the genetic information at gene
information at gene
information at gene what happens is when a gene is expressed
what happens is when a gene is expressed
what happens is when a gene is expressed it makes a photocopy and so you get an
it makes a photocopy and so you get an
it makes a photocopy and so you get an RNA copy a message copy that contains
RNA copy a message copy that contains
RNA copy a message copy that contains blocks of coding sequence separated by
blocks of coding sequence separated by
blocks of coding sequence separated by the yellow non-coding sequence and this
the yellow non-coding sequence and this
the yellow non-coding sequence and this is happening for almost all of our
is happening for almost all of our
is happening for almost all of our 23,000 genes that have this particular
23,000 genes that have this particular
23,000 genes that have this particular structure they go through this
structure they go through this
structure they go through this arrangement and for this gene to be
arrangement and for this gene to be
arrangement and for this gene to be expressed and then read you take out the
expressed and then read you take out the
expressed and then read you take out the yellow bits and this is a process called
yellow bits and this is a process called
yellow bits and this is a process called splicing it brings it together so that’s
splicing it brings it together so that’s
splicing it brings it together so that’s a mature gene message every time a cell
a mature gene message every time a cell
a mature gene message every time a cell divides all that genetic material has to
divides all that genetic material has to
divides all that genetic material has to be copied and DNA replication it’s
be copied and DNA replication it’s
be copied and DNA replication it’s pretty good but it’s not perfect
pretty good but it’s not perfect
pretty good but it’s not perfect mistakes happen just look around the
mistakes happen just look around the
mistakes happen just look around the room everyone is different we all have
room everyone is different we all have
room everyone is different we all have the same genes but we have subtle
the same genes but we have subtle
the same genes but we have subtle variations that affect eye color here
variations that affect eye color here
variations that affect eye color here height metabolism and so on and a lot of
height metabolism and so on and a lot of
height metabolism and so on and a lot of the DNA changes won’t make any
the DNA changes won’t make any
the DNA changes won’t make any difference but when they occur in an
difference but when they occur in an
difference but when they occur in an important gene then there can be
important gene then there can be
important gene then there can be problems so in the example here we’ve
problems so in the example here we’ve
problems so in the example here we’ve got a spelling error in the DNA the red
got a spelling error in the DNA the red
got a spelling error in the DNA the red block that carries through to the
block that carries through to the
block that carries through to the messenger RNA and then when that is
messenger RNA and then when that is
messenger RNA and then when that is spliced the message downstream of the
spliced the message downstream of the
spliced the message downstream of the mutation is corrupted so it’s like
mutation is corrupted so it’s like
mutation is corrupted so it’s like reading a book you’ve got a massive book
reading a book you’ve got a massive book
reading a book you’ve got a massive book of instructions you’re halfway through
of instructions you’re halfway through
of instructions you’re halfway through it and it says stop reading the rest the
it and it says stop reading the rest the
it and it says stop reading the rest the message might be there be another letter
message might be there be another letter
message might be there be another letter read beyond that point this is the
read beyond that point this is the
read beyond that point this is the normal perfect human DNA but everyone in
normal perfect human DNA but everyone in
normal perfect human DNA but everyone in this room is carrying one to two lethal
this room is carrying one to two lethal
this room is carrying one to two lethal gene mutations well I mean lethal either
gene mutations well I mean lethal either
gene mutations well I mean lethal either incompatible with life where it’s going
incompatible with life where it’s going
incompatible with life where it’s going to result in a severe disease it’s quite
to result in a severe disease it’s quite
to result in a severe disease it’s quite scary the examples here we’ve got the
scary the examples here we’ve got the
scary the examples here we’ve got the little red lightning bolts showing where
little red lightning bolts showing where
little red lightning bolts showing where particular mutations could occur but
particular mutations could occur but
particular mutations could occur but you’ll see that you have a defective
you’ll see that you have a defective
you’ll see that you have a defective copy in one chromosome but the other
copy in one chromosome but the other
copy in one chromosome but the other parent has given a copy that is working
parent has given a copy that is working
parent has given a copy that is working so this is why you’re here and on the X
so this is why you’re here and on the X
so this is why you’re here and on the X chromosome
chromosome
chromosome women have two copies so they can carry
women have two copies so they can carry
women have two copies so they can carry a defective copy of a gene and there’s a
a defective copy of a gene and there’s a
a defective copy of a gene and there’s a backup copy however if a boy inherits a
backup copy however if a boy inherits a
backup copy however if a boy inherits a defective gene on the X chromosome
defective gene on the X chromosome
defective gene on the X chromosome there’s no backup copy and this leads to
there’s no backup copy and this leads to
there’s no backup copy and this leads to what’s called an x-linked recessive
what’s called an x-linked recessive
what’s called an x-linked recessive disease now the one I’ve been spending
disease now the one I’ve been spending
disease now the one I’ve been spending too much my life on is a condition
too much my life on is a condition
too much my life on is a condition called Duchenne muscular dystrophy now
called Duchenne muscular dystrophy now
called Duchenne muscular dystrophy now this is such a cruel devastating disease
this is such a cruel devastating disease
this is such a cruel devastating disease on so many fronts
on so many fronts
on so many fronts one in three cases is a new mutation
one in three cases is a new mutation
one in three cases is a new mutation that is the gene is very error-prone
that is the gene is very error-prone
that is the gene is very error-prone it’s an accident waiting to happen
it’s an accident waiting to happen
it’s an accident waiting to happen the boys are born they look normal and
the boys are born they look normal and
the boys are born they look normal and that is because the protein that is
that is because the protein that is
that is because the protein that is responsible for this disease normally
responsible for this disease normally
responsible for this disease normally give strength and stability to the
give strength and stability to the
give strength and stability to the muscle fibers in the absence of a
muscle fibers in the absence of a
muscle fibers in the absence of a functional protein the muscles break
functional protein the muscles break
functional protein the muscles break down faster than they should so when the
down faster than they should so when the
down faster than they should so when the boys are young the muscle growth is
boys are young the muscle growth is
boys are young the muscle growth is keeping up with the degeneration and so
keeping up with the degeneration and so
keeping up with the degeneration and so for the first few years they’re not so
for the first few years they’re not so
for the first few years they’re not so bad one of the early symptoms you’ll
bad one of the early symptoms you’ll
bad one of the early symptoms you’ll have enlarged curves and the parents
have enlarged curves and the parents
have enlarged curves and the parents think fantastic we’re gonna have a
think fantastic we’re gonna have a
think fantastic we’re gonna have a sportsman here a real athlete those in
sportsman here a real athlete those in
sportsman here a real athlete those in large cow market of muscle damage the
large cow market of muscle damage the
large cow market of muscle damage the muscles been replaced with fat and
muscles been replaced with fat and
muscles been replaced with fat and connective tissue as the disease
connective tissue as the disease
connective tissue as the disease progresses the boys get weaker and
progresses the boys get weaker and
progresses the boys get weaker and weaker they’re in a wheelchair by the
weaker they’re in a wheelchair by the
weaker they’re in a wheelchair by the age of 12 most commonly in the absence
age of 12 most commonly in the absence
age of 12 most commonly in the absence of good healthcare 90% would die before
of good healthcare 90% would die before
of good healthcare 90% would die before they were 20 from cardiac and
they were 20 from cardiac and
they were 20 from cardiac and respiratory complications to become too
respiratory complications to become too
respiratory complications to become too weak to just breathe speaking of some of
weak to just breathe speaking of some of
weak to just breathe speaking of some of the parents they described this as a
the parents they described this as a
the parents they described this as a death by a thousand cuts the gene was
death by a thousand cuts the gene was
death by a thousand cuts the gene was identified in 1986 and they were
identified in 1986 and they were
identified in 1986 and they were confident claims that gene therapy
confident claims that gene therapy
confident claims that gene therapy replacing the gene could work or stem
replacing the gene could work or stem
replacing the gene could work or stem cell therapy or even muscle cell therapy
cell therapy or even muscle cell therapy
cell therapy or even muscle cell therapy could work the various technical reasons
could work the various technical reasons
could work the various technical reasons these haven’t come through well it’s
these haven’t come through well it’s
these haven’t come through well it’s over 20 years ago I came up this crazy
over 20 years ago I came up this crazy
over 20 years ago I came up this crazy idea instead of trying to replace the
idea instead of trying to replace the
idea instead of trying to replace the gene or add new cells what if we try and
gene or add new cells what if we try and
gene or add new cells what if we try and repair the expression of the damaged
repair the expression of the damaged
repair the expression of the damaged gene and so here we go with a defective
gene and so here we go with a defective
gene and so here we go with a defective gene message and we’ve come up with a
gene message and we’ve come up with a
gene message and we’ve come up with a compound a genetic drug at the chemistry
compound a genetic drug at the chemistry
compound a genetic drug at the chemistry name
name
name fostro downright morpholino all your
fostro downright morpholino all your
fostro downright morpholino all your nucleotide there’ll be a test at the end
nucleotide there’ll be a test at the end
nucleotide there’ll be a test at the end for people to spell this so the way this
for people to spell this so the way this
for people to spell this so the way this works is like a paintbrush
works is like a paintbrush
works is like a paintbrush it actually masks over that affected
it actually masks over that affected
it actually masks over that affected part of the message so when it’s brought
part of the message so when it’s brought
part of the message so when it’s brought together all of a sudden we restore a
together all of a sudden we restore a
together all of a sudden we restore a shorter message so going back to the
shorter message so going back to the
shorter message so going back to the book analogy you’ve come to the fact
book analogy you’ve come to the fact
book analogy you’ve come to the fact that says stop reading you basically
that says stop reading you basically
that says stop reading you basically tear that page out or cover it with
tear that page out or cover it with
tear that page out or cover it with whiteout you then go on to the rest of
whiteout you then go on to the rest of
whiteout you then go on to the rest of the story you might miss a little bit in
the story you might miss a little bit in
the story you might miss a little bit in the middle but you’ve got the ends the
the middle but you’ve got the ends the
the middle but you’ve got the ends the beginning and the end of the store and
beginning and the end of the store and
beginning and the end of the store and that’s the crucial thing just glossing
that’s the crucial thing just glossing
that’s the crucial thing just glossing over 20 years of hard lab work with a
over 20 years of hard lab work with a
over 20 years of hard lab work with a very dedicated team we were designing
very dedicated team we were designing
very dedicated team we were designing different types of paintbrushes looking
different types of paintbrushes looking
different types of paintbrushes looking at different spelling errors and the
at different spelling errors and the
at different spelling errors and the gene to work out where to put these
gene to work out where to put these
gene to work out where to put these compounds we’ve worked on animal models
compounds we’ve worked on animal models
compounds we’ve worked on animal models we worked on human cells and we’ve come
we worked on human cells and we’ve come
we worked on human cells and we’ve come up with a compound there’s been in
up with a compound there’s been in
up with a compound there’s been in clinical trials now this has been in
clinical trials now this has been in
clinical trials now this has been in clinical trials in the states for the
clinical trials in the states for the
clinical trials in the states for the trials running for about five years and
trials running for about five years and
trials running for about five years and this is a young lead for Billy now Billy
this is a young lead for Billy now Billy
this is a young lead for Billy now Billy is at this stage thirteen years old two
is at this stage thirteen years old two
is at this stage thirteen years old two years before this he couldn’t walk up or
years before this he couldn’t walk up or
years before this he couldn’t walk up or down this path and just listen to the
down this path and just listen to the
down this path and just listen to the next bit
he’s walking uphill and whistling so his
he’s walking uphill and whistling so his breathing has stabilized last year he
breathing has stabilized last year he
breathing has stabilized last year he actually finished the Pittsburgh
actually finished the Pittsburgh
actually finished the Pittsburgh children’s marathon he was 14 years old
and it was then complaining that they
and it was then complaining that they weren’t playing Chariots of Fire as he
weren’t playing Chariots of Fire as he
weren’t playing Chariots of Fire as he crossed I mean he is 15 going on 40 but
crossed I mean he is 15 going on 40 but
crossed I mean he is 15 going on 40 but he is an amazing kid
he is an amazing kid
he is an amazing kid now for this drug to go to other boys we
now for this drug to go to other boys we
now for this drug to go to other boys we had to have approval from the Food and
had to have approval from the Food and
had to have approval from the Food and Drug Administration the US FDA and I’m
Drug Administration the US FDA and I’m
Drug Administration the US FDA and I’m delighted relieved ecstatic numb that
delighted relieved ecstatic numb that
delighted relieved ecstatic numb that less than a month ago approval was given
maybe this is just what I’m hoping is
maybe this is just what I’m hoping is going to be the first of a new type of
going to be the first of a new type of
going to be the first of a new type of genetic drug there are 7,000 inherited
genetic drug there are 7,000 inherited
genetic drug there are 7,000 inherited diseases described and there’s the
diseases described and there’s the
diseases described and there’s the potential for this type of therapy to be
potential for this type of therapy to be
potential for this type of therapy to be applied to many many different mutations
applied to many many different mutations
applied to many many different mutations the type of spelling error that affects
the type of spelling error that affects
the type of spelling error that affects splicing is estimated to be between 10
splicing is estimated to be between 10
splicing is estimated to be between 10 and 20 percent across all the mutations
and 20 percent across all the mutations
and 20 percent across all the mutations this type of therapy is applicable to
this type of therapy is applicable to
this type of therapy is applicable to many many different conditions so we’re
many many different conditions so we’re
many many different conditions so we’re working on spinal muscular atrophy we’re
working on spinal muscular atrophy we’re
working on spinal muscular atrophy we’re working on cystic fibrosis pompes
working on cystic fibrosis pompes
working on cystic fibrosis pompes disease Huntington’s disease 30 a
disease Huntington’s disease 30 a
disease Huntington’s disease 30 a scapula humeral muscular dystrophy
scapula humeral muscular dystrophy
scapula humeral muscular dystrophy another test on that name as well and
another test on that name as well and
another test on that name as well and the reason you get into medical research
the reason you get into medical research
the reason you get into medical research is to try and make a difference and I’ll
is to try and make a difference and I’ll
is to try and make a difference and I’ll just show this video of a young lad
just show this video of a young lad
just show this video of a young lad called Aidan Aidan at the start of the
called Aidan Aidan at the start of the
called Aidan Aidan at the start of the trial since the frustration Aidan’s just
trial since the frustration Aidan’s just
trial since the frustration Aidan’s just over 12 years old then four months into
over 12 years old then four months into
over 12 years old then four months into the treatment okay so you can get into a
the treatment okay so you can get into a
the treatment okay so you can get into a car now and the last one I’ll just leave
car now and the last one I’ll just leave
car now and the last one I’ll just leave you with I want to look at the
you with I want to look at the
you with I want to look at the expression on his face and his mother’s
expression on his face and his mother’s
expression on his face and his mother’s voice
this is over 20 years of work isn’t that
this is over 20 years of work isn’t that you’ve done here must be really hard and
you’ve done here must be really hard and
you’ve done here must be really hard and been working with a with a large team
been working with a with a large team
been working with a with a large team I’ve got a fantastic group of people
I’ve got a fantastic group of people
I’ve got a fantastic group of people I’ve got knowledge sue Fletcher Abbi
I’ve got knowledge sue Fletcher Abbi
I’ve got knowledge sue Fletcher Abbi Adams kangri
Adams kangri
Adams kangri Kristen West they’ve got a fantastic
Kristen West they’ve got a fantastic
Kristen West they’ve got a fantastic research team at Murdoch at the moment
research team at Murdoch at the moment
research team at Murdoch at the moment and they were there a privilege to work
and they were there a privilege to work
and they were there a privilege to work with and the colleagues overseas and how
with and the colleagues overseas and how
with and the colleagues overseas and how hard was it to get the FDA approval
hard was it to get the FDA approval
hard was it to get the FDA approval because this is something this is the
because this is something this is the
because this is something this is the first type of it’s drug ever released it
first type of it’s drug ever released it
first type of it’s drug ever released it or ever approved it’s the first
or ever approved it’s the first
or ever approved it’s the first phosphoramidite morpholino
phosphoramidite morpholino
phosphoramidite morpholino oligonucleotide ever approved it’s the
oligonucleotide ever approved it’s the
oligonucleotide ever approved it’s the first destroyin restoring drug that has
first destroyin restoring drug that has
first destroyin restoring drug that has shown an unequivocal increase in the
shown an unequivocal increase in the
shown an unequivocal increase in the missing protein after treatment it’s the
missing protein after treatment it’s the
missing protein after treatment it’s the first by switching compound that I’m
first by switching compound that I’m
first by switching compound that I’m aware of that has been approved that
aware of that has been approved that
aware of that has been approved that this is a specific compound that’s been
this is a specific compound that’s been
this is a specific compound that’s been approved I don’t know ever stated here
approved I don’t know ever stated here
approved I don’t know ever stated here but are we talking about you know a new
but are we talking about you know a new
but are we talking about you know a new type of mitts I would like to think that
type of mitts I would like to think that
type of mitts I would like to think that this has enormous applications in so
this has enormous applications in so
this has enormous applications in so many different conditions from the size
many different conditions from the size
many different conditions from the size of this room we would have I’m guessing
of this room we would have I’m guessing
of this room we would have I’m guessing 50 to 60 people who are carriers of the
50 to 60 people who are carriers of the
50 to 60 people who are carriers of the cystic fibrosis defect chain there are
cystic fibrosis defect chain there are
cystic fibrosis defect chain there are 40 people in here at least who are
40 people in here at least who are
40 people in here at least who are missing the spinal muscular atrophy
missing the spinal muscular atrophy
missing the spinal muscular atrophy janessa min 1 this is going to become
janessa min 1 this is going to become
janessa min 1 this is going to become hopefully a personalized treatment the
hopefully a personalized treatment the
hopefully a personalized treatment the thing is we’ve got a huge genome
thing is we’ve got a huge genome
thing is we’ve got a huge genome spelling errors at different parts
spelling errors at different parts
spelling errors at different parts whatare goal was to come up with the
whatare goal was to come up with the
whatare goal was to come up with the paint brushes that will sort of fix the
paint brushes that will sort of fix the
paint brushes that will sort of fix the different parts so this is hopefully
different parts so this is hopefully
different parts so this is hopefully going to be a new type of personalized
going to be a new type of personalized
going to be a new type of personalized medicine it’s extraordinary
medicine it’s extraordinary
medicine it’s extraordinary congratulations to you and the team
congratulations to you and the team
congratulations to you and the team [Applause]
[Applause]
[Applause] [Music]
[Music]
[Music] [Applause]
[Applause]
[Applause] you
you
you [Music]
”
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