A brave new future for science beyond traditional animal models
raise your hand
if someone you know has suffered with
alzheimer’s
how about heart disease
cancer
stroke
that’s a lot of hands
the standard approach for tackling
diseases like this is to use
animal models for drug discovery and
testing
but what if i told you that 95
of drugs tested in animals actually fail
in humans biomedical research
is in a translation crisis but how did
we get here
i’m elizabeth ormandy and i’ve spent the
last 15 years
unraveling our animal-based science
systems
what i’ve come to learn is that we need
to change the way science is taught
practiced and regulated
today i invite you to come on a journey
that explores
the persistent use of animal models why
they are failing
and what we can do and it all starts
way back in your childhood with a
science education practice
that at first glance might seem
unrelated
now raise your hand if you did animal
dissection
in your school science classes
most of you and so our story begins
there is a deeply held assumption that
traditional animal dissection is the
best way
to learn anatomy and body systems so
dissection remains prevalent
in our schools and universities however
there is compelling evidence to show
that
non-animal teaching methods like virtual
anatomy tools
are better for education less costly
for school budgets safer and more
inclusive for students
and they’re the greener option in terms
of their environmental impact
they are also the ethical option
and here’s why there are three
principles that guide
the ethical use of animals in science
and science education and they’re called
the three
r’s replacement reduction refinement
i’m going to zero in on replacement for
a moment
this principle tells us that if we can
meet our scientific
or educational goals without using
animals
it is an ethical obligation to use
non-animal methods
empirical data from the last 15 years
shows that 90 of students
do just as well and in most cases
better when they use non-animal teaching
methods compared
to dissection so under the principle of
replacement
dissection should have ended 10 years
ago case closed
but here’s the rub science teachers are
not taught about the three r’s
in their teacher training programs and
students are not taught about the three
r’s
in early science education so
the harmful and unnecessary practice of
dissection
persists so we need to change
how science is taught in two key ways
first by ending the unnecessary practice
of dissection
second by making sure that the three r’s
are taught and adhered to
in early science education and by doing
so
i think that we can avoid scenes like
this
where animal life is taken for no
discernible educational benefit
and what’s more this animal life is
being disrespected
instead i believe that we can raise a
generation of young scientists
who are encouraged to lean into the
natural
empathy and compassion that they have
for animals
rather than being asked to dissociate
themselves from these qualities in the
name of science
so in 2018 i established canada’s first
humane science education program
this program teaches k-12 life science
education
including internal anatomy without using
a single
real animal and here’s what humane
science education looks like
we use virtual anatomy tools these
beautiful
paper dissections plastic anatomy models
and augmented and virtual reality
technology
but what does any of this have to do
with the failure of animal models in
drug development
well i’ve come to learn that it’s all
about the prevailing
science culture
i want you to imagine that you are back
in grade six you’ve just done a frog
dissection and you were kind of grossed
out
but your scientific curiosity won the
day
fast forward to grade 12 and this time
you want to opt out of doing the fetal
pig dissection
but your teacher strongly encourages you
to take part
she knows that you want to go on and do
biology at university
so you do dissection for the second time
you go on to your chosen undergraduate
degree then a master’s degree
and a phd all the while
you carry with you an implicit
assumption
that the right way the best way to do
science is to kill animals and take them
apart
no one along the way challenges that
assumption
and in fact since grade six you’ve been
taught that animal models are the gold
standard and that using them in science
is a necessary evil
you are now a lead principal
investigator
you have your own lab you’re studying
alzheimer’s and you’re using
mice for research and drug development
you get government grants you test one
experimental drug
after another you kill hundreds of mice
time passes five years
ten years fifteen
you make no new breakthroughs
animal models of alzheimer’s fail close
to 100
of the time and in fact data from a
range of different biomedical
disciplines studying sepsis stroke
multiple sclerosis hiv aids heart
disease
depression asthma cancer and so on
show that on average 95
of drugs tested in animals go on to fail
in human clinical trials 95
think of all those tax dollars all those
animals all those
failed patients for few to no
new treatments
since grade six you’ve been taught that
animal models are the gold
standard in science
they’re not they’re failing us
but why well there are two
main reasons the first relates to sloppy
science practices
the second relates to insurmountable
species differences
so let me talk about sloppy science for
a minute
there’s a phenomenon called confirmation
bias
and this describes a tendency to seek
out
or give greater weight to data points
that confirm
hypotheses there are two
important experimental techniques for
avoiding
confirmation bias and they’re called
randomization
and blinding in the context of
animal-based research
randomization is when researchers
randomly allocate
animals to different treatment groups
blinding
is when researchers do not know which
animal received which treatment
now there is evidence to show that
researchers who
use animal models for drug development
in many cases are not using
randomization
and blinding so they’re not controlling
for confirmation bias
what this means is that in studies with
no randomization
and no blinding there is a significant
and inaccurate overestimate of the
clinical effect of a drug
researchers are finding their desired
clinical
outcome where there is none because they
did not control for confirmation bias
and it is inaccurate data like this that
is used to make decisions
about whether novel drugs are advanced
to clinical trials in humans and in many
cases
ineffective drugs are permitted to
proceed
now this is not a new-found phenomenon
this has been well documented
since at least the late 1990s
but despite this particular sloppy
science practice being highlighted
more than two decades ago a report from
just this year showed that more than 90
percent of animal studies
exploring new drugs for covert 19
failed to report blinding
so we really need to change our science
practices and make sure
that experimental techniques to control
bias are used
every single time
lives quite literally depend on it
the second and most important reason
that animal models fail
is because animals often don’t make good
stand-ins for humans
so even if we did the most rigorous
animal-based studies with all the
randomization and all the blinding
in many cases species differences simply
cannot be overcome
so what can we do then if animals
don’t make good models for human biology
well there are groundbreaking human
relevant
non-animal methods that are being
developed and they overcome
species differences by using human cells
and human tissues that can be collected
non-invasively and with consent
and i have a few favorites to share with
you
organs on a chip this is the lung on a
chip developed
at harvard’s vice institute and the
channels in the chip
have living human lung cells on one side
and capillary blood vessel cells
on the other so despite appearances
the chip mimics functional human lung
tissue
this device has been used to identify
new disease biomarkers
and it can be used to develop new
treatments for conditions like chronic
obstructive pulmonary disorder
and asthma and there are other chips
heart on a chip liver on a chip
blood-brain barrier
on a chip and there are researchers who
are linking chips together
to observe multi-system effects in human
cells and human tissues
there are organoids these are miniature
functional organ units that grow
into 3d spherical shapes
the ones pictured here are brain
organoids and they’ve been used by
researchers to better understand autism
and schizophrenia most recently
brain organoids were used to explore the
neurobiological impact
of covid19
and there are other organoids intestinal
kidney ovarian and many more
this is a 3d bioprinter it works much
the same as the 3d
printers that you’re probably more used
to the ones that use plastic polymers
but instead bioprinters use something
called bioink
which contains human cells so as it
prints
cells are layered and they can be
printed into
3d functional human tissue
3d bioprinters have been used to print
small sections
of human trachea that’s the windpipe to
study
chronic obstructive pulmonary disorder
they’ve been used to print neural tissue
to study neurodegenerative disorders
and to study spinal cord injury
and there are many more applications as
well
relevant non-animal technologies like
these are changing the shape of
changing the face of science in profound
ways however they are not being taught
to our undergraduate science students in
any meaningful
or systematic way i wanted to change
that
so i created and now teach canada’s
first
undergraduate science course that is
fully focused on non-animal methods in
biomedical science
and my hope is that talented young
scientists will carry this knowledge
forward
and will shift their own science
practices in favor of non-animal methods
progress on the development and
adoption of non-animal technologies is
being made primarily in countries that
have
a legislative foundation governing the
use of animals in science
so for example in the european union
all eu member states answer to the eu
directive
on the protection of animals used for
scientific purposes
that directive is very clear that the
ultimate goal
is the replacement of animals in science
in canada we have no such legislation
and i firmly believe that this lack of a
legislative framework
is hindering some much-needed progress
here
so we need to change how animal-based
science is governed
and move towards a legislated system one
which
prioritizes non-animal methods by
codifying replacement into law
but one that also ensures that any
remaining animal-based science is held
to much more rigorous standards than we
are currently seeing and i’m deeply
committed to being on the forefront of
that conversation
so to recap we need to change science
education
we need to end the unnecessary practice
of dissection we need to make sure that
the three r’s are taught and adhered to
in early science education and we need
to make sure that our undergraduate
students are being taught about
non-animal methods
we need to change how science is
practiced
and include much more rigorous
experimental design in animal studies
but most importantly make sure that
non-animal methods are being made top
priority and that starts with our
research funders
and we need to change how animal-based
science is regulated and move towards a
legislative system
in 2015 together with some incredible
colleagues we co-founded canada’s first
charity that works solely on the issues
that i’ve presented here today
we are called the society for humane
science
and i could not be more proud of the
work that we do
in my closing moments with you i want to
leave you with this
even though you may never have
heard about these issues before they
affect you and you’re part of them
through everything from
the taxes that you pay which fund animal
research
to the medical or chemical products that
you purchase or interact with on a daily
basis
to the loved ones you’ve lost because of
failed animal experiments
and i know that pain well i’ve lost them
too
my hope here today is that i’ve inspired
you
to research these issues for yourself to
get curious about science education and
how drugs are developed
and to start exercising your voice where
you can
because we are called on to do nothing
short of changing science culture
and while there is indeed a growing
global movement
that seeks to achieve better science
without animals we cannot do that
without collective political will
i can’t do that without you
thank you