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