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