[Applause] she after dogs they were the next
she after dogs they were the next
she after dogs they were the next species to be domesticated so we
species to be domesticated so we
species to be domesticated so we understand them very well we’ve used
understand them very well we’ve used
understand them very well we’ve used them for thousands of years we know how
them for thousands of years we know how
them for thousands of years we know how to breed them we know how to manage them
to breed them we know how to manage them
to breed them we know how to manage them but when it comes to research there are
but when it comes to research there are
but when it comes to research there are forgotten species we use mice for
forgotten species we use mice for
forgotten species we use mice for research we use monkeys why don’t we use
research we use monkeys why don’t we use
research we use monkeys why don’t we use sheep so for most of my research career
sheep so for most of my research career
sheep so for most of my research career I’ve actually used laboratory mice and
I’ve actually used laboratory mice and
I’ve actually used laboratory mice and I’ve studied motor function cognitive
I’ve studied motor function cognitive
I’ve studied motor function cognitive function sleep circadian rhythms and
function sleep circadian rhythms and
function sleep circadian rhythms and mice but about 10 years ago I decided to
mice but about 10 years ago I decided to
mice but about 10 years ago I decided to switch tags and change species this was
switch tags and change species this was
switch tags and change species this was not a decision that I took lightly
not a decision that I took lightly
not a decision that I took lightly because not only did I not own any sheep
because not only did I not own any sheep
because not only did I not own any sheep I’ve never used sheep and I despite
I’ve never used sheep and I despite
I’ve never used sheep and I despite being a New Zealand ER I didn’t know
being a New Zealand ER I didn’t know
being a New Zealand ER I didn’t know very much about them and sheep not used
very much about them and sheep not used
very much about them and sheep not used as a cognitive species there are no
as a cognitive species there are no
as a cognitive species there are no cognitive tasks devised for sheep at one
cognitive tasks devised for sheep at one
cognitive tasks devised for sheep at one level this is the sheeps own fault
level this is the sheeps own fault
level this is the sheeps own fault because if you take a look at sheep you
because if you take a look at sheep you
because if you take a look at sheep you don’t immediately go hmm
don’t immediately go hmm
don’t immediately go hmm that’s an ideal species for modeling
that’s an ideal species for modeling
that’s an ideal species for modeling human cognition
human cognition
human cognition most people think sheep are stupid and
most people think sheep are stupid and
most people think sheep are stupid and think that they’re as stupid as they
think that they’re as stupid as they
think that they’re as stupid as they look but it wasn’t just an image problem
look but it wasn’t just an image problem
look but it wasn’t just an image problem that I had with thinking about using
that I had with thinking about using
that I had with thinking about using sheep when I came to look at how to
sheep when I came to look at how to
sheep when I came to look at how to measure a behaviors in sheep I found
measure a behaviors in sheep I found
measure a behaviors in sheep I found nothing had been done on this that there
nothing had been done on this that there
nothing had been done on this that there were no measures for quantifying
were no measures for quantifying
were no measures for quantifying behavior and sheep and if you can’t
behavior and sheep and if you can’t
behavior and sheep and if you can’t quantify the outcome measures of an
quantify the outcome measures of an
quantify the outcome measures of an animal model you can’t use it for a
animal model you can’t use it for a
animal model you can’t use it for a research okay let me wind back a bit for
research okay let me wind back a bit for
research okay let me wind back a bit for the past 25 years I’ve been working on a
the past 25 years I’ve been working on a
the past 25 years I’ve been working on a progressive neurological disease
progressive neurological disease
progressive neurological disease Huntington’s disease this is a
Huntington’s disease this is a
Huntington’s disease this is a devastating disorder that starts with
devastating disorder that starts with
devastating disorder that starts with insidious motor loss of motor control
insidious motor loss of motor control
insidious motor loss of motor control cognitive decline personality changes
cognitive decline personality changes
cognitive decline personality changes but a progressive progresses
but a progressive progresses
but a progressive progresses relentlessly and eventually it destroys
relentlessly and eventually it destroys
relentlessly and eventually it destroys the life of the sufferer by end stage
the life of the sufferer by end stage
the life of the sufferer by end stage and a Huntington’s patient is unable to
and a Huntington’s patient is unable to
and a Huntington’s patient is unable to move unable to think unable to make
move unable to think unable to make
move unable to think unable to make decisions and this takes a terrible toll
decisions and this takes a terrible toll
decisions and this takes a terrible toll not just on the patient but also on
not just on the patient but also on
not just on the patient but also on their family so this photograph shows
their family so this photograph shows
their family so this photograph shows two people whose lives have been changed
two people whose lives have been changed
two people whose lives have been changed forever by Huntington’s disease on the
forever by Huntington’s disease on the
forever by Huntington’s disease on the left is my friend child sir bean so
left is my friend child sir bean so
left is my friend child sir bean so Charles was a frontline war
Charles was a frontline war
Charles was a frontline war correspondent for NBC when he learned
correspondent for NBC when he learned
correspondent for NBC when he learned that his father had been diagnosed with
that his father had been diagnosed with
that his father had been diagnosed with Huntington’s disease his brother John on
Huntington’s disease his brother John on
Huntington’s disease his brother John on the right was a prominent lawyer once
the right was a prominent lawyer once
the right was a prominent lawyer once described as the finest mind of his
described as the finest mind of his
described as the finest mind of his generation at Oxford but both men
generation at Oxford but both men
generation at Oxford but both men unfortunately inherited the Huntington’s
unfortunately inherited the Huntington’s
unfortunately inherited the Huntington’s disease from their father and you can
disease from their father and you can
disease from their father and you can see the toll that this has taken on on
see the toll that this has taken on on
see the toll that this has taken on on John already this photograph was taken
John already this photograph was taken
John already this photograph was taken in 2010 John’s now completely bedridden
in 2010 John’s now completely bedridden
in 2010 John’s now completely bedridden unable to communicate and our neighbor
unable to communicate and our neighbor
unable to communicate and our neighbor and requires 24-hour care Charles is not
and requires 24-hour care Charles is not
and requires 24-hour care Charles is not affected by the disease yet but he will
affected by the disease yet but he will
affected by the disease yet but he will be he’s carries a gene he will get
be he’s carries a gene he will get
be he’s carries a gene he will get Huntington’s disease and worse for
Huntington’s disease and worse for
Huntington’s disease and worse for Charles is that he’s seen his father’s
Charles is that he’s seen his father’s
Charles is that he’s seen his father’s decline and he’s seen his brother’s
decline and he’s seen his brother’s
decline and he’s seen his brother’s decline and he knows that that is his
decline and he knows that that is his
decline and he knows that that is his future so without research there is no
future so without research there is no
future so without research there is no hope for patients with Huntington’s
hope for patients with Huntington’s
hope for patients with Huntington’s disease and for people who carry the
disease and for people who carry the
disease and for people who carry the Huntington’s disease gene so I had three
Huntington’s disease gene so I had three
Huntington’s disease gene so I had three reasons for working on on Huntington’s
reasons for working on on Huntington’s
reasons for working on on Huntington’s disease first was the development of an
disease first was the development of an
disease first was the development of an HD model a large animal model of sheep
HD model a large animal model of sheep
HD model a large animal model of sheep previously the only models available to
previously the only models available to
previously the only models available to us had been mice the second reason was
us had been mice the second reason was
us had been mice the second reason was that sheep live for a long time so they
that sheep live for a long time so they
that sheep live for a long time so they have long lives and mice only lived for
have long lives and mice only lived for
have long lives and mice only lived for two years so modeling a disease that is
two years so modeling a disease that is
two years so modeling a disease that is a late onset adult onset disease in a
a late onset adult onset disease in a
a late onset adult onset disease in a mouse that only lives for two years is
mouse that only lives for two years is
mouse that only lives for two years is very limiting sheep don’t live as long
very limiting sheep don’t live as long
very limiting sheep don’t live as long as humans obviously but they can easily
as humans obviously but they can easily
as humans obviously but they can easily live for 10 years
live for 10 years
live for 10 years and so having this long life gives us a
and so having this long life gives us a
and so having this long life gives us a unique window of opportunity for
unique window of opportunity for
unique window of opportunity for studying particularly the early stages
studying particularly the early stages
studying particularly the early stages of Huntington’s disease and the third
of Huntington’s disease and the third
of Huntington’s disease and the third reason was that sheep have large brains
reason was that sheep have large brains
reason was that sheep have large brains this photograph shows an image of a
this photograph shows an image of a
this photograph shows an image of a mouse brain a sheep brain and a human
mouse brain a sheep brain and a human
mouse brain a sheep brain and a human brain and if you can see the mouse brain
brain and if you can see the mouse brain
brain and if you can see the mouse brain at the bottom is obvious which of these
at the bottom is obvious which of these
at the bottom is obvious which of these is a better species to model the human
is a better species to model the human
is a better species to model the human the sheep in the middle obviously it’s
the sheep in the middle obviously it’s
the sheep in the middle obviously it’s not just the size difference is that the
not just the size difference is that the
not just the size difference is that the anatomy is much more similar in the
anatomy is much more similar in the
anatomy is much more similar in the Sheep to the human than as the mouse so
Sheep to the human than as the mouse so
Sheep to the human than as the mouse so large brain long life and a Huntingdon’s
large brain long life and a Huntingdon’s
large brain long life and a Huntingdon’s disease sheep model but that wasn’t the
disease sheep model but that wasn’t the
disease sheep model but that wasn’t the end of the problem in fact it was just
end of the problem in fact it was just
end of the problem in fact it was just the beginning because we didn’t have
the beginning because we didn’t have
the beginning because we didn’t have methods for quantifying sheep behavior
methods for quantifying sheep behavior
methods for quantifying sheep behavior the fact that sheep were thought of as
the fact that sheep were thought of as
the fact that sheep were thought of as being stupid didn’t bother me
being stupid didn’t bother me
being stupid didn’t bother me particularly after all I worked on mice
particularly after all I worked on mice
particularly after all I worked on mice and mice not the most intelligent of
and mice not the most intelligent of
and mice not the most intelligent of species but one thing that I was told is
species but one thing that I was told is
species but one thing that I was told is that I wouldn’t be able to work with
that I wouldn’t be able to work with
that I wouldn’t be able to work with sheep alone and if you can’t work with
sheep alone and if you can’t work with
sheep alone and if you can’t work with an animal alone you can’t do behavioral
an animal alone you can’t do behavioral
an animal alone you can’t do behavioral testings through human your neuro
testings through human your neuro
testings through human your neuro psychological testing and animal
psychological testing and animal
psychological testing and animal behavior is done with the investigator
behavior is done with the investigator
behavior is done with the investigator and either the person alone or just with
and either the person alone or just with
and either the person alone or just with one person so if I couldn’t work with
one person so if I couldn’t work with
one person so if I couldn’t work with the Sheep alone I wouldn’t be able to do
the Sheep alone I wouldn’t be able to do
the Sheep alone I wouldn’t be able to do the sort of tests that I wanted to do
the sort of tests that I wanted to do
the sort of tests that I wanted to do well thankfully this Dogma turned out
well thankfully this Dogma turned out
well thankfully this Dogma turned out not to be true not only a sheep good
not to be true not only a sheep good
not to be true not only a sheep good expects for cognitive function and
expects for cognitive function and
expects for cognitive function and they’re actually very smart much smarter
they’re actually very smart much smarter
they’re actually very smart much smarter than we’d thought they in comparable
than we’d thought they in comparable
than we’d thought they in comparable tasks their performances as good as that
tasks their performances as good as that
tasks their performances as good as that of a monkey but it also turned out that
of a monkey but it also turned out that
of a monkey but it also turned out that they were very willing to work alone as
they were very willing to work alone as
they were very willing to work alone as long as they were with an investigator
long as they were with an investigator
long as they were with an investigator that they trusted and this willingness
that they trusted and this willingness
that they trusted and this willingness meant that we could devise tasks for
meant that we could devise tasks for
meant that we could devise tasks for measuring cognitive function that were
measuring cognitive function that were
measuring cognitive function that were really relevant to Huntington’s disease
really relevant to Huntington’s disease
really relevant to Huntington’s disease I’m going to show you this rather than
I’m going to show you this rather than
I’m going to show you this rather than tell you how easy it is for sheep to do
tell you how easy it is for sheep to do
tell you how easy it is for sheep to do performances I’m going to show you a
performances I’m going to show you a
performances I’m going to show you a short video so this sheep is in an arena
short video so this sheep is in an arena
short video so this sheep is in an arena she’s working by herself there is an
she’s working by herself there is an
she’s working by herself there is an investor
investor
investor later at the back but she actually runs
later at the back but she actually runs
later at the back but she actually runs this experiment herself she comes
this experiment herself she comes
this experiment herself she comes through a corridor breaks a beam and the
through a corridor breaks a beam and the
through a corridor breaks a beam and the two stimuli come up on the on the screen
two stimuli come up on the on the screen
two stimuli come up on the on the screen now this sheeps been taught to recognize
now this sheeps been taught to recognize
now this sheeps been taught to recognize the faces of familiar individuals Emma
the faces of familiar individuals Emma
the faces of familiar individuals Emma Watson on the right and in this
Watson on the right and in this
Watson on the right and in this particular case so what she does is she
particular case so what she does is she
particular case so what she does is she comes up she looks at the faces she
comes up she looks at the faces she
comes up she looks at the faces she makes a decision and she indicates this
makes a decision and she indicates this
makes a decision and she indicates this decision by breaking an infrared beam
decision by breaking an infrared beam
decision by breaking an infrared beam that goes from the top of the screen to
that goes from the top of the screen to
that goes from the top of the screen to the bottom she breaks it with her nose
the bottom she breaks it with her nose
the bottom she breaks it with her nose if she gets it right a food reward is
if she gets it right a food reward is
if she gets it right a food reward is delivered to the hopper if she gets it
delivered to the hopper if she gets it
delivered to the hopper if she gets it wrong there’s a tone sounds and she has
wrong there’s a tone sounds and she has
wrong there’s a tone sounds and she has to start over again so let’s just run
to start over again so let’s just run
to start over again so let’s just run the video and you can see her doing this
the video and you can see her doing this
the video and you can see her doing this task yourself they’ve got it right and
task yourself they’ve got it right and
task yourself they’ve got it right and she’s eating her food so the willingness
she’s eating her food so the willingness
she’s eating her food so the willingness to work like this that you can do so not
to work like this that you can do so not
to work like this that you can do so not just the face recognition tasks that
just the face recognition tasks that
just the face recognition tasks that you’ve seen but other tasks of cognitive
you’ve seen but other tasks of cognitive
you’ve seen but other tasks of cognitive flexibility means that we now have the
flexibility means that we now have the
flexibility means that we now have the tools to measure behavioral and
tools to measure behavioral and
tools to measure behavioral and cognitive changes in the Huntington’s
cognitive changes in the Huntington’s
cognitive changes in the Huntington’s disease sheep obviously we’re not just
disease sheep obviously we’re not just
disease sheep obviously we’re not just interested in sheep intelligence we want
interested in sheep intelligence we want
interested in sheep intelligence we want to use these models to test new
to use these models to test new
to use these models to test new therapies and and the prospect of being
therapies and and the prospect of being
therapies and and the prospect of being able to test and quantify changes means
able to test and quantify changes means
able to test and quantify changes means that we have ways of assessing
that we have ways of assessing
that we have ways of assessing therapeutic knuth new therapies this
therapeutic knuth new therapies this
therapeutic knuth new therapies this gives great hope to Huntington’s
gives great hope to Huntington’s
gives great hope to Huntington’s patients who need who desperately need
patients who need who desperately need
patients who need who desperately need these sort of treatments but it’s not
these sort of treatments but it’s not
these sort of treatments but it’s not just Huntington’s patients for whom
just Huntington’s patients for whom
just Huntington’s patients for whom there can be new hope there are at least
there can be new hope there are at least
there can be new hope there are at least 16 different sheep versions of
16 different sheep versions of
16 different sheep versions of neurological diseases so this is this is
neurological diseases so this is this is
neurological diseases so this is this is a list of just some of them most of
a list of just some of them most of
a list of just some of them most of these diseases are actually extremely
these diseases are actually extremely
these diseases are actually extremely rare you might not have heard of many of
rare you might not have heard of many of
rare you might not have heard of many of them and so you might think well they
them and so you might think well they
them and so you might think well they don’t really matter that much they only
don’t really matter that much they only
don’t really matter that much they only affect a few people but you try telling
affect a few people but you try telling
affect a few people but you try telling that to the mother of a child who’s
that to the mother of a child who’s
that to the mother of a child who’s demented because it has battens disease
demented because it has battens disease
demented because it has battens disease for every person who has
for every person who has
for every person who has one of these rare diseases research is
one of these rare diseases research is
one of these rare diseases research is essential to give them hope and we don’t
essential to give them hope and we don’t
essential to give them hope and we don’t need to use scarce resources on a rare
need to use scarce resources on a rare
need to use scarce resources on a rare disease developing new mouse models of
disease developing new mouse models of
disease developing new mouse models of these disease the sheep models already
these disease the sheep models already
these disease the sheep models already exists so we should be using sheep
exists so we should be using sheep
exists so we should be using sheep models to study these disorders
models to study these disorders
models to study these disorders especially now we have ways of of
especially now we have ways of of
especially now we have ways of of measuring particularly cognitive decline
measuring particularly cognitive decline
measuring particularly cognitive decline and it’s not just these rare genetic
and it’s not just these rare genetic
and it’s not just these rare genetic diseases that sheep get sheep get
diseases that sheep get sheep get
diseases that sheep get sheep get epilepsy sheep had brain tumors sheep
epilepsy sheep had brain tumors sheep
epilepsy sheep had brain tumors sheep gets strokes sheep have sheep get
gets strokes sheep have sheep get
gets strokes sheep have sheep get depressed we could use sheep as research
depressed we could use sheep as research
depressed we could use sheep as research models for many of these diseases which
models for many of these diseases which
models for many of these diseases which is so difficult to model in mice so that
is so difficult to model in mice so that
is so difficult to model in mice so that even that doesn’t have to be the end of
even that doesn’t have to be the end of
even that doesn’t have to be the end of the story it could be just the beginning
the story it could be just the beginning
the story it could be just the beginning the the sheep models these sheep models
the the sheep models these sheep models
the the sheep models these sheep models were not discovered by a careful
were not discovered by a careful
were not discovered by a careful selected examination of the sheep
selected examination of the sheep
selected examination of the sheep population they were discovered
population they were discovered
population they were discovered serendipitously by observant farmers and
serendipitously by observant farmers and
serendipitously by observant farmers and scientists what might we see if we
scientists what might we see if we
scientists what might we see if we actually look for new models so
actually look for new models so
actually look for new models so Alzheimer’s and Parkinson’s disease for
Alzheimer’s and Parkinson’s disease for
Alzheimer’s and Parkinson’s disease for example these these diseases are set to
example these these diseases are set to
example these these diseases are set to become a major problem in the next in
become a major problem in the next in
become a major problem in the next in the next few decades as our population
the next few decades as our population
the next few decades as our population ages and current mouse models are
ages and current mouse models are
ages and current mouse models are inadequate not only it’s not just a
inadequate not only it’s not just a
inadequate not only it’s not just a short life of mouse models that make
short life of mouse models that make
short life of mouse models that make them inadequate for modeling Alzheimer’s
them inadequate for modeling Alzheimer’s
them inadequate for modeling Alzheimer’s disease for example the mice don’t make
disease for example the mice don’t make
disease for example the mice don’t make the right pathology so the parks the
the right pathology so the parks the
the right pathology so the parks the neurofibrillary tangles that
neurofibrillary tangles that
neurofibrillary tangles that characterize Alzheimer’s disease mice
characterize Alzheimer’s disease mice
characterize Alzheimer’s disease mice don’t get them but sheep do you look at
don’t get them but sheep do you look at
don’t get them but sheep do you look at an old sheep and they have tangles not
an old sheep and they have tangles not
an old sheep and they have tangles not as many as you do an Alzheimer’s disease
as many as you do an Alzheimer’s disease
as many as you do an Alzheimer’s disease but they they definitely have them they
but they they definitely have them they
but they they definitely have them they also have amyloid pathology so if we
also have amyloid pathology so if we
also have amyloid pathology so if we looked perhaps we might find that out
looked perhaps we might find that out
looked perhaps we might find that out there there’s already a good large
there there’s already a good large
there there’s already a good large animal model of Alzheimer’s disease so
animal model of Alzheimer’s disease so
animal model of Alzheimer’s disease so what can we learn from sheep well I
what can we learn from sheep well I
what can we learn from sheep well I think we’re limited by our own ambition
think we’re limited by our own ambition
think we’re limited by our own ambition sheep have been the patient servant of
sheep have been the patient servant of
sheep have been the patient servant of humankind for
humankind for
humankind for thousands of years and if we could
thousands of years and if we could
thousands of years and if we could abandon our prejudices about them and
abandon our prejudices about them and
abandon our prejudices about them and embrace their potential they could have
embrace their potential they could have
embrace their potential they could have a lot more to offer us as large animal
a lot more to offer us as large animal
a lot more to offer us as large animal models of the human euro degenerative
models of the human euro degenerative
models of the human euro degenerative diseases for which we so desperately
diseases for which we so desperately
diseases for which we so desperately need treatments
need treatments
need treatments [Applause]
”
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