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Fighting Brain Diseases with Worms | Alex Parker | TEDxMontreal


[Music]

[Music] [Applause]

[Applause]

[Applause] so how many of you here played with bugs

so how many of you here played with bugs

so how many of you here played with bugs or slimy creatures as a kid yeah okay me

or slimy creatures as a kid yeah okay me

or slimy creatures as a kid yeah okay me too and like my daughter I was more

too and like my daughter I was more

too and like my daughter I was more interested in finding fish bait than

interested in finding fish bait than

interested in finding fish bait than actually fishing but as an adult the

actually fishing but as an adult the

actually fishing but as an adult the most you might come across these

most you might come across these

most you might come across these creatures is in your compost when my son

creatures is in your compost when my son

creatures is in your compost when my son started school last year

started school last year

started school last year he was asked what your parents do for a

he was asked what your parents do for a

he was asked what your parents do for a living and he said my dad plays with

living and he said my dad plays with

living and he said my dad plays with worms so there are many things that live

worms so there are many things that live

worms so there are many things that live undetected by us out in your backyard

undetected by us out in your backyard

undetected by us out in your backyard this is my backyard in the soil in the

this is my backyard in the soil in the

this is my backyard in the soil in the compost but out there is an animal

compost but out there is an animal

compost but out there is an animal species that lives a great success and

species that lives a great success and

species that lives a great success and it’s nearly invisible to us all so what

it’s nearly invisible to us all so what

it’s nearly invisible to us all so what am I talking about worms but not

am I talking about worms but not

am I talking about worms but not earthworms that you would use for

earthworms that you would use for

earthworms that you would use for fishing or you will find on the sidewalk

fishing or you will find on the sidewalk

fishing or you will find on the sidewalk after it rains

after it rains

after it rains they’re called nematodes microscopic

they’re called nematodes microscopic

they’re called nematodes microscopic worm species that’s barely visible to

worm species that’s barely visible to

worm species that’s barely visible to your eyes and they’re everywhere it’s

your eyes and they’re everywhere it’s

your eyes and they’re everywhere it’s been said that if you could eliminate

been said that if you could eliminate

been said that if you could eliminate all matter on the planet except for

all matter on the planet except for

all matter on the planet except for nematodes you would still see a ghostly

nematodes you would still see a ghostly

nematodes you would still see a ghostly outline of the world because they’re

outline of the world because they’re

outline of the world because they’re everywhere would you believe that

everywhere would you believe that

everywhere would you believe that playing with things from the compost

playing with things from the compost

playing with things from the compost could help stop brain diseases what if

could help stop brain diseases what if

could help stop brain diseases what if there’s a worm species that could stop

there’s a worm species that could stop

there’s a worm species that could stop you from getting sick the worm that

you from getting sick the worm that

you from getting sick the worm that could do this is called Caenorhabditis

could do this is called Caenorhabditis

could do this is called Caenorhabditis elegans or C elegans – its friends it’s

elegans or C elegans – its friends it’s

elegans or C elegans – its friends it’s very small it’s only one millimetre long

very small it’s only one millimetre long

very small it’s only one millimetre long when it’s fully grown and these are some

when it’s fully grown and these are some

when it’s fully grown and these are some worms in captivity crawling across a

worms in captivity crawling across a

worms in captivity crawling across a dish in the laboratory so barely visible

dish in the laboratory so barely visible

dish in the laboratory so barely visible to your eyes this is the army of tiny

to your eyes this is the army of tiny

to your eyes this is the army of tiny worms that researchers worldwide used to

worms that researchers worldwide used to

worms that researchers worldwide used to answer many big questions things like

answer many big questions things like

answer many big questions things like how do cells develop into whole animals

how do cells develop into whole animals

how do cells develop into whole animals how do cells die

how do cells die

how do cells die they’ve even provided clues into how we

they’ve even provided clues into how we

they’ve even provided clues into how we age and why would people use these worms

age and why would people use these worms

age and why would people use these worms well there are many benefits first

well there are many benefits first

well there are many benefits first silicon’s has rudimentary features in

silicon’s has rudimentary features in

silicon’s has rudimentary features in common with humans has a nervous system

common with humans has a nervous system

common with humans has a nervous system it has reproductive system as muscle

it has reproductive system as muscle

it has reproductive system as muscle cells and intestine things like that

cells and intestine things like that

cells and intestine things like that they also have a really short rapid life

they also have a really short rapid life

they also have a really short rapid life cycle

cycle

cycle which means you can do experiments in a

which means you can do experiments in a

which means you can do experiments in a short amount of time from a couple of

short amount of time from a couple of

short amount of time from a couple of days to a few weeks you can also grow

days to a few weeks you can also grow

days to a few weeks you can also grow them a large numbers which means you can

them a large numbers which means you can

them a large numbers which means you can use many animals over and over again and

use many animals over and over again and

use many animals over and over again and many experiments you have confidence in

many experiments you have confidence in

many experiments you have confidence in your results a cool feature of these

your results a cool feature of these

your results a cool feature of these animals is that they’re transparent

animals is that they’re transparent

animals is that they’re transparent which means that the microscope you can

which means that the microscope you can

which means that the microscope you can look directly inside living animals

look directly inside living animals

look directly inside living animals now this transparency is very useful for

now this transparency is very useful for

now this transparency is very useful for color coding experiments where with the

color coding experiments where with the

color coding experiments where with the right animals you can look at individual

right animals you can look at individual

right animals you can look at individual tissues and cells in living aging

tissues and cells in living aging

tissues and cells in living aging animals word experiments are inexpensive

animals word experiments are inexpensive

animals word experiments are inexpensive and when you’re done with them you can

and when you’re done with them you can

and when you’re done with them you can put them in the freezer until you need

put them in the freezer until you need

put them in the freezer until you need them again that’s not something I’d

them again that’s not something I’d

them again that’s not something I’d recommend for other animals like your

recommend for other animals like your

recommend for other animals like your pets if you go on vacation it’s not the

pets if you go on vacation it’s not the

pets if you go on vacation it’s not the same thing so these animals are

same thing so these animals are

same thing so these animals are important component of your backyard

important component of your backyard

important component of your backyard ecosystem but they’ve made important

ecosystem but they’ve made important

ecosystem but they’ve made important contributions to human health as well so

contributions to human health as well so

contributions to human health as well so my laboratory here in Montreal at the

my laboratory here in Montreal at the

my laboratory here in Montreal at the Sierra Shoom University Mario we study a

Sierra Shoom University Mario we study a

Sierra Shoom University Mario we study a degenerative disease called amyotrophic

degenerative disease called amyotrophic

degenerative disease called amyotrophic lateral sclerosis or ALS is also known

lateral sclerosis or ALS is also known

lateral sclerosis or ALS is also known as Lou Gehrig’s disease you may be

as Lou Gehrig’s disease you may be

as Lou Gehrig’s disease you may be familiar with it from the ice bucket

familiar with it from the ice bucket

familiar with it from the ice bucket challenge it’s past few summers it’s a

challenge it’s past few summers it’s a

challenge it’s past few summers it’s a pretty bad disease where otherwise

pretty bad disease where otherwise

pretty bad disease where otherwise healthy people are quickly struck down

healthy people are quickly struck down

healthy people are quickly struck down what happens is a part of the nervous

what happens is a part of the nervous

what happens is a part of the nervous system that’s required for movement

system that’s required for movement

system that’s required for movement begins to die and with it the patients

begins to die and with it the patients

begins to die and with it the patients and it can happen fast anywhere from a

and it can happen fast anywhere from a

and it can happen fast anywhere from a few months to a few years after

few months to a few years after

few months to a few years after diagnosis and there’s no cure so what

diagnosis and there’s no cure so what

diagnosis and there’s no cure so what does this have to do with worms

does this have to do with worms

does this have to do with worms well worms like people can get sick too

well worms like people can get sick too

well worms like people can get sick too and maybe this can help you or your

and maybe this can help you or your

and maybe this can help you or your family so what do worms do in nature

family so what do worms do in nature

family so what do worms do in nature they work hard to find food and

they work hard to find food and

they work hard to find food and reproduce and they’re very good at it

reproduce and they’re very good at it

reproduce and they’re very good at it but we wanted to give them a new job so

but we wanted to give them a new job so

but we wanted to give them a new job so researchers using modern genetic

researchers using modern genetic

researchers using modern genetic technologies have discovered over a

technologies have discovered over a

technologies have discovered over a dozen genes that when there’s a mutation

dozen genes that when there’s a mutation

dozen genes that when there’s a mutation one of these genes will cause ALS now

one of these genes will cause ALS now

one of these genes will cause ALS now this is good because then they can study

this is good because then they can study

this is good because then they can study what these genes are doing normally and

what these genes are doing normally and

what these genes are doing normally and what goes wrong in ALS patients so our

what goes wrong in ALS patients so our

what goes wrong in ALS patients so our approach is simple since a single

approach is simple since a single

approach is simple since a single mutation one of these genes causes ALS

mutation one of these genes causes ALS

mutation one of these genes causes ALS what happens if we take these human

what happens if we take these human

what happens if we take these human genes put them into the worms and we’ve

genes put them into the worms and we’ve

genes put them into the worms and we’ve done that when put ALS genes into worms

done that when put ALS genes into worms

done that when put ALS genes into worms do they get sick this is not great for

do they get sick this is not great for

do they get sick this is not great for them

them

them but it provides us with a very powerful

but it provides us with a very powerful

but it provides us with a very powerful research tool so what does this look

research tool so what does this look

research tool so what does this look like well here’s a worm on a plate in

like well here’s a worm on a plate in

like well here’s a worm on a plate in the lab minding its own business

the lab minding its own business

the lab minding its own business until a student comes along and caps it

until a student comes along and caps it

until a student comes along and caps it on the head gap and it moves away

on the head gap and it moves away

on the head gap and it moves away because who likes being tapped on the

because who likes being tapped on the

because who likes being tapped on the head this this is normal but when you do

head this this is normal but when you do

head this this is normal but when you do this with one with the ALS worms same

this with one with the ALS worms same

this with one with the ALS worms same experiment tap nothing happens this

experiment tap nothing happens this

experiment tap nothing happens this animal is very sick it’s essentially

animal is very sick it’s essentially

animal is very sick it’s essentially paralyzed and it can just barely move

paralyzed and it can just barely move

paralyzed and it can just barely move its head so as a researcher this sick

its head so as a researcher this sick

its head so as a researcher this sick worm is easy to see and it’s something

worm is easy to see and it’s something

worm is easy to see and it’s something we can work with I mentioned before that

we can work with I mentioned before that

we can work with I mentioned before that in ALS it’s the neurons involved in

in ALS it’s the neurons involved in

in ALS it’s the neurons involved in movement

movement

movement more specifically the motor neurons

more specifically the motor neurons

more specifically the motor neurons these are the neurons that end up dying

these are the neurons that end up dying

these are the neurons that end up dying into patients is this what we see in our

into patients is this what we see in our

into patients is this what we see in our simple animal model well they’re

simple animal model well they’re

simple animal model well they’re transparent so we can look the red

transparent so we can look the red

transparent so we can look the red signals are the are the worms motor

signals are the are the worms motor

signals are the are the worms motor neurons and if you wait long enough it

neurons and if you wait long enough it

neurons and if you wait long enough it takes about a week you will see that

takes about a week you will see that

takes about a week you will see that these neurons do begin to die maybe in a

these neurons do begin to die maybe in a

these neurons do begin to die maybe in a way similar to what happens in ALS so

way similar to what happens in ALS so

way similar to what happens in ALS so what are we trying to do here we now

what are we trying to do here we now

what are we trying to do here we now essentially have a hospital full of sick

essentially have a hospital full of sick

essentially have a hospital full of sick worms right so maybe we can use them to

worms right so maybe we can use them to

worms right so maybe we can use them to find for example drugs to help ALS

find for example drugs to help ALS

find for example drugs to help ALS patients so as you may appreciate

patients so as you may appreciate

patients so as you may appreciate contemporary drug discovery is expensive

contemporary drug discovery is expensive

contemporary drug discovery is expensive takes a long time billions of dollars

takes a long time billions of dollars

takes a long time billions of dollars many years to bring a single drug to

many years to bring a single drug to

many years to bring a single drug to market even testing one molecule and a

market even testing one molecule and a

market even testing one molecule and a good model like a mouse takes a long

good model like a mouse takes a long

good model like a mouse takes a long time and it’s expensive maybe we can use

time and it’s expensive maybe we can use

time and it’s expensive maybe we can use our worms of some sort of advanced scout

our worms of some sort of advanced scout

our worms of some sort of advanced scout system to find drugs and maybe find good

system to find drugs and maybe find good

system to find drugs and maybe find good drugs that have an increased chance of

drugs that have an increased chance of

drugs that have an increased chance of working down the road in patients and

working down the road in patients and

working down the road in patients and we’ve done this using our ALS worms

we’ve done this using our ALS worms

we’ve done this using our ALS worms we developed a rapid drug screening

we developed a rapid drug screening

we developed a rapid drug screening technique where we find drugs that make

technique where we find drugs that make

technique where we find drugs that make the worms healthy again so how does this

the worms healthy again so how does this

the worms healthy again so how does this work well I showed you before that worms

work well I showed you before that worms

work well I showed you before that worms like the crawl that do it outside in the

like the crawl that do it outside in the

like the crawl that do it outside in the soil or in the lab on plates but they

soil or in the lab on plates but they

soil or in the lab on plates but they can also swim if you put them in a bath

can also swim if you put them in a bath

can also swim if you put them in a bath they start moving like crazy these are

they start moving like crazy these are

they start moving like crazy these are regular worms I put them in a bath and

regular worms I put them in a bath and

regular worms I put them in a bath and they’re thrashing about very active

they’re thrashing about very active

they’re thrashing about very active healthy worms but when you make the ALS

healthy worms but when you make the ALS

healthy worms but when you make the ALS warm swim they get tired very quickly

warm swim they get tired very quickly

warm swim they get tired very quickly and stop moving I realize this is a

and stop moving I realize this is a

and stop moving I realize this is a movie of worms not really moving but if

movie of worms not really moving but if

movie of worms not really moving but if you look carefully you can see that some

you look carefully you can see that some

you look carefully you can see that some of them are barely twitching in any

of them are barely twitching in any

of them are barely twitching in any event they’re very sick in

event they’re very sick in

event they’re very sick in while so compared to this it’s very easy

while so compared to this it’s very easy

while so compared to this it’s very easy to see or find drugs that make them

to see or find drugs that make them

to see or find drugs that make them better again so these are the ALS worms

better again so these are the ALS worms

better again so these are the ALS worms the same ones treated with a drug and

the same ones treated with a drug and

the same ones treated with a drug and they’re moving like crazy they’re

they’re moving like crazy they’re

they’re moving like crazy they’re healthy they’re essentially been rescued

healthy they’re essentially been rescued

healthy they’re essentially been rescued and this is the basis of the drug

and this is the basis of the drug

and this is the basis of the drug screening technique we’re looking for

screening technique we’re looking for

screening technique we’re looking for this worms that move like crazy so with

this worms that move like crazy so with

this worms that move like crazy so with this approach we can now test many

this approach we can now test many

this approach we can now test many molecules in a short amount of time and

molecules in a short amount of time and

molecules in a short amount of time and it’s cheap it costs $1 to know if any

it’s cheap it costs $1 to know if any

it’s cheap it costs $1 to know if any particular drug is worth investigating

particular drug is worth investigating

particular drug is worth investigating further as a potential therapeutic all

further as a potential therapeutic all

further as a potential therapeutic all right so we went ahead and did this and

right so we went ahead and did this and

right so we went ahead and did this and with this approach we screened thousands

with this approach we screened thousands

with this approach we screened thousands of drugs in our worms and we found about

of drugs in our worms and we found about

of drugs in our worms and we found about 20 molecules that made them healthy

20 molecules that made them healthy

20 molecules that made them healthy again it may be cool to cure worms but

again it may be cool to cure worms but

again it may be cool to cure worms but this is not our goal we want to help

this is not our goal we want to help

this is not our goal we want to help patients but as you can imagine no one

patients but as you can imagine no one

patients but as you can imagine no one is going to take advice from a worm

is going to take advice from a worm

is going to take advice from a worm doctor right there’s no way so we have

doctor right there’s no way so we have

doctor right there’s no way so we have to be very sure of a results before you

to be very sure of a results before you

to be very sure of a results before you get anywhere near people so this means

get anywhere near people so this means

get anywhere near people so this means we have to test these drugs in models

we have to test these drugs in models

we have to test these drugs in models closer to humans so to do this we ask

closer to humans so to do this we ask

closer to humans so to do this we ask colleagues for help but where do you go

colleagues for help but where do you go

colleagues for help but where do you go from worms why not fish so a local

from worms why not fish so a local

from worms why not fish so a local colleague has developed a fish model of

colleague has developed a fish model of

colleague has developed a fish model of ALS specifically a zebrafish model and

ALS specifically a zebrafish model and

ALS specifically a zebrafish model and they tested our group of molecules in

they tested our group of molecules in

they tested our group of molecules in their fish and they found one compound

their fish and they found one compound

their fish and they found one compound which was very potent now this is

which was very potent now this is

which was very potent now this is interesting because this is a drug

interesting because this is a drug

interesting because this is a drug that’s been around for a long time and

that’s been around for a long time and

that’s been around for a long time and it’s been used to treat things like

it’s been used to treat things like

it’s been used to treat things like schizophrenia so we’re happy about this

schizophrenia so we’re happy about this

schizophrenia so we’re happy about this and this we wanted to go on so we’re

and this we wanted to go on so we’re

and this we wanted to go on so we’re eager to test this drug and what’s

eager to test this drug and what’s

eager to test this drug and what’s considered the gold standard animal

considered the gold standard animal

considered the gold standard animal model of ALS it’s a mouse model so again

model of ALS it’s a mouse model so again

model of ALS it’s a mouse model so again with a local colleague they tested this

with a local colleague they tested this

with a local colleague they tested this drug and it worked so now we’re very

drug and it worked so now we’re very

drug and it worked so now we’re very excited this drug now works in three

excited this drug now works in three

excited this drug now works in three animal models we know a lot about this

animal models we know a lot about this

animal models we know a lot about this compound and that it’s safe for humans

compound and that it’s safe for humans

compound and that it’s safe for humans this meant there’s a chance we could get

this meant there’s a chance we could get

this meant there’s a chance we could get it to humans in a clinical trial for ALS

it to humans in a clinical trial for ALS

it to humans in a clinical trial for ALS so we attracted lucky they get the

so we attracted lucky they get the

so we attracted lucky they get the attention of a clinical researcher here

attention of a clinical researcher here

attention of a clinical researcher here in Canada as well and his team set up a

in Canada as well and his team set up a

in Canada as well and his team set up a small clinical trial to test this drug

small clinical trial to test this drug

small clinical trial to test this drug in ALS and we waited because he knows

in ALS and we waited because he knows

in ALS and we waited because he knows you may appreciate

you may appreciate

you may appreciate doing this type of stuff in humans takes

doing this type of stuff in humans takes

doing this type of stuff in humans takes longer than playing with worms right

longer than playing with worms right

longer than playing with worms right and it’s a little stressful for

and it’s a little stressful for

and it’s a little stressful for everybody in the lab because you’re

everybody in the lab because you’re

everybody in the lab because you’re waiting what if it doesn’t work whatever

waiting what if it doesn’t work whatever

waiting what if it doesn’t work whatever this drugs only works in these small

this drugs only works in these small

this drugs only works in these small animal models what if our models are

animal models what if our models are

animal models what if our models are wrong but in science when you find

wrong but in science when you find

wrong but in science when you find something interesting it means very

something interesting it means very

something interesting it means very little if others can’t replicate your

little if others can’t replicate your

little if others can’t replicate your work or find something similar in their

work or find something similar in their

work or find something similar in their laboratories so you have to test it also

laboratories so you have to test it also

laboratories so you have to test it also as you may appreciate science is a

as you may appreciate science is a

as you may appreciate science is a collaborative effort but it’s also very

collaborative effort but it’s also very

collaborative effort but it’s also very competitive what if another group

competitive what if another group

competitive what if another group publishes something similar to us before

publishes something similar to us before

publishes something similar to us before us and you know the careers of

us and you know the careers of

us and you know the careers of professors students postdoctoral fellows

professors students postdoctoral fellows

professors students postdoctoral fellows throw that line the balance being first

throw that line the balance being first

throw that line the balance being first is very important but we are patient and

is very important but we are patient and

is very important but we are patient and we waited and after much excellent hard

we waited and after much excellent hard

we waited and after much excellent hard work the results are promising and now a

work the results are promising and now a

work the results are promising and now a large country countrywide clinical trial

large country countrywide clinical trial

large country countrywide clinical trial to test this drug in ALS will go ahead

to test this drug in ALS will go ahead

to test this drug in ALS will go ahead so if you step back it looks like we

so if you step back it looks like we

so if you step back it looks like we basically short-circuited the drug

basically short-circuited the drug

basically short-circuited the drug discovery system we’ve took a drug that

discovery system we’ve took a drug that

discovery system we’ve took a drug that we found in worms and moved it to a

we found in worms and moved it to a

we found in worms and moved it to a clinical trial in two years and it

clinical trial in two years and it

clinical trial in two years and it didn’t cost very much so we’ll wait and

didn’t cost very much so we’ll wait and

didn’t cost very much so we’ll wait and see and even better is the fact that the

see and even better is the fact that the

see and even better is the fact that the results are promising and we’re now

results are promising and we’re now

results are promising and we’re now applying this approach to other diseases

applying this approach to other diseases

applying this approach to other diseases things like Alzheimer’s disease and

things like Alzheimer’s disease and

things like Alzheimer’s disease and dementia so insights into human health

dementia so insights into human health

dementia so insights into human health can come from unlikely places your

can come from unlikely places your

can come from unlikely places your backyard now playing with things taking

backyard now playing with things taking

backyard now playing with things taking risks so this year when when my son

risks so this year when when my son

risks so this year when when my son started school and he was asked what his

started school and he was asked what his

started school and he was asked what his parents did for a living he said my dad

parents did for a living he said my dad

parents did for a living he said my dad makes worm sick then he makes them

makes worm sick then he makes them

makes worm sick then he makes them better again and maybe one day this can

better again and maybe one day this can

better again and maybe one day this can be OK for people to thank

be OK for people to thank

be OK for people to thank [Applause]

”

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