Beyond Brain Surgery | Peter Dirks | TEDxBranksomeHall

well hello it’s great to be here I’m

well hello it’s great to be here I’m going to tell you a story today that

going to tell you a story today that

going to tell you a story today that intersects my life in brain surgery

intersects my life in brain surgery

intersects my life in brain surgery neural stem cells and brain cancer and I

neural stem cells and brain cancer and I

neural stem cells and brain cancer and I call it beyond brain surgery and I think

call it beyond brain surgery and I think

call it beyond brain surgery and I think beyond brain surgery is science and

beyond brain surgery is science and

beyond brain surgery is science and biology and that’s the future in my

biology and that’s the future in my

biology and that’s the future in my daily work I get to see the human the

daily work I get to see the human the

daily work I get to see the human the live human brain almost every day and

live human brain almost every day and

live human brain almost every day and every day I’m absolutely marveled at how

every day I’m absolutely marveled at how

every day I’m absolutely marveled at how this tan-colored three-pound organ

dictates and is embedded within our

dictates and is embedded within our feelings our emotions our skills our

feelings our emotions our skills our

feelings our emotions our skills our knowledge how is it that biological

knowledge how is it that biological

knowledge how is it that biological pulsating tissue can be the essence of

pulsating tissue can be the essence of

pulsating tissue can be the essence of who we are and certainly I love this

who we are and certainly I love this

who we are and certainly I love this quote from this physicist this

quote from this physicist this

quote from this physicist this theoretical physicist from the US who

theoretical physicist from the US who

theoretical physicist from the US who says who says the human brain is a

says who says the human brain is a

says who says the human brain is a hundred billion neurons each neuron

hundred billion neurons each neuron

hundred billion neurons each neuron connected to 10,000 other neurons and

connected to 10,000 other neurons and

connected to 10,000 other neurons and and sitting on your shoulders is the

and sitting on your shoulders is the

and sitting on your shoulders is the most complicated object in the known

most complicated object in the known

most complicated object in the known universe just the complexity of the

universe just the complexity of the

universe just the complexity of the human brain is absolutely astounding and

human brain is absolutely astounding and

human brain is absolutely astounding and 200 years ago we had a simple view of

200 years ago we had a simple view of

200 years ago we had a simple view of what was going on the brain based on

what was going on the brain based on

what was going on the brain based on examination of patience and

examination of patience and

examination of patience and understanding of cos that affected them

understanding of cos that affected them

understanding of cos that affected them and affected their functions and then

and affected their functions and then

and affected their functions and then studying their brains after to see which

studying their brains after to see which

studying their brains after to see which which regions were involved and so we

which regions were involved and so we

which regions were involved and so we had this map for for movement of

had this map for for movement of

had this map for for movement of different parts of the body and

different parts of the body and

different parts of the body and different areas of feeling but now with

different areas of feeling but now with

different areas of feeling but now with functional MRI with diffusion tensor

functional MRI with diffusion tensor

functional MRI with diffusion tensor imaging we have an exquisite map of we

imaging we have an exquisite map of we

imaging we have an exquisite map of we can obtain an exquisite map for every

can obtain an exquisite map for every

can obtain an exquisite map for every person’s brain and it’s not that a text

person’s brain and it’s not that a text

person’s brain and it’s not that a text book can’t tell the story of each

book can’t tell the story of each

book can’t tell the story of each person’s brain we need to actually write

person’s brain we need to actually write

person’s brain we need to actually write a text book for each individual person’s

a text book for each individual person’s

a text book for each individual person’s brain and here you can see all the

brain and here you can see all the

brain and here you can see all the different bundles of nerves that are can

different bundles of nerves that are can

different bundles of nerves that are can interconnecting throughout a human brain

interconnecting throughout a human brain

interconnecting throughout a human brain and as well Jeffrey Lichtman from

and as well Jeffrey Lichtman from

and as well Jeffrey Lichtman from Harvard University has devised a method

Harvard University has devised a method

Harvard University has devised a method in animals where he can label individual

in animals where he can label individual

in animals where he can label individual neurons with different colors to study

neurons with different colors to study

neurons with different colors to study the the cell the cell connectivity of

the the cell the cell connectivity of

the the cell the cell connectivity of the of the brain and certainly these

the of the brain and certainly these

the of the brain and certainly these approaches will come to humans in the

approaches will come to humans in the

approaches will come to humans in the future but this is changing the way we

future but this is changing the way we

future but this is changing the way we think about how these different circuits

think about how these different circuits

think about how these different circuits define the essence of who we are and how

define the essence of who we are and how

define the essence of who we are and how we function now as a neurosurgeon we’re

we function now as a neurosurgeon we’re

we function now as a neurosurgeon we’re not we’re not quite at the cellular

not we’re not quite at the cellular

not we’re not quite at the cellular level but certainly these advances in

level but certainly these advances in

level but certainly these advances in technology are enabling us to do brain

technology are enabling us to do brain

technology are enabling us to do brain surgery safer than we’ve ever been able

surgery safer than we’ve ever been able

surgery safer than we’ve ever been able to do before and we can take this

to do before and we can take this

to do before and we can take this information not just the anatomy not

information not just the anatomy not

information not just the anatomy not just the shape of the brain but we can

just the shape of the brain but we can

just the shape of the brain but we can take these maps of the different

take these maps of the different

take these maps of the different functions for these four for example we

functions for these four for example we

functions for these four for example we can take language and we can pinpoint

can take language and we can pinpoint

can take language and we can pinpoint where language is in the brain so we

where language is in the brain so we

where language is in the brain so we know if we have a lesion to remove in

know if we have a lesion to remove in

know if we have a lesion to remove in the brain we can go around the language

the brain we can go around the language

the brain we can go around the language area to remove the lesion and keep the

area to remove the lesion and keep the

area to remove the lesion and keep the person’s language functions intact and

person’s language functions intact and

person’s language functions intact and we can integrate this with computer

we can integrate this with computer

we can integrate this with computer systems so when we’re doing surgery we

systems so when we’re doing surgery we

systems so when we’re doing surgery we can point to areas in the head or in the

can point to areas in the head or in the

can point to areas in the head or in the brain that tell us exactly where we are

brain that tell us exactly where we are

brain that tell us exactly where we are with respect to the imaging and the

with respect to the imaging and the

with respect to the imaging and the different functional pathways that we

different functional pathways that we

different functional pathways that we want to protect and preserve and so

want to protect and preserve and so

want to protect and preserve and so here’s here’s us we were pointing at the

here’s here’s us we were pointing at the

here’s here’s us we were pointing at the brain in that patient and this tells us

brain in that patient and this tells us

brain in that patient and this tells us relative to the scan where we are and

relative to the scan where we are and

relative to the scan where we are and here just at the bottom left is a tumor

here just at the bottom left is a tumor

here just at the bottom left is a tumor deep in this person’s brain that we’re

deep in this person’s brain that we’re

deep in this person’s brain that we’re seeking to remove and so this is

seeking to remove and so this is

seeking to remove and so this is incredible technology it’s advancing all

incredible technology it’s advancing all

incredible technology it’s advancing all the time it’s allowing us to to devise

the time it’s allowing us to to devise

the time it’s allowing us to to devise safe and better access to make brain

safe and better access to make brain

safe and better access to make brain surgery a safer and safer and and as

surgery a safer and safer and and as

surgery a safer and safer and and as well we have microscopes that allow us

well we have microscopes that allow us

well we have microscopes that allow us to operate at at a millimeter by

to operate at at a millimeter by

to operate at at a millimeter by millimeter level so I could spend four

millimeter level so I could spend four

millimeter level so I could spend four hours in an area the size of the end of

hours in an area the size of the end of

hours in an area the size of the end of my thumb to remove a tumor for example

my thumb to remove a tumor for example

my thumb to remove a tumor for example and and carefully tease it away from

and and carefully tease it away from

and and carefully tease it away from from nerves that might be responsible

from nerves that might be responsible

from nerves that might be responsible for

for

for a person swallowing or their ability to

a person swallowing or their ability to

a person swallowing or their ability to speak for example so all of these tools

speak for example so all of these tools

speak for example so all of these tools we have now at our disposal some brain

we have now at our disposal some brain

we have now at our disposal some brain surgery has never been safer and so it

surgery has never been safer and so it

surgery has never been safer and so it allows us to confront a very difficult

allows us to confront a very difficult

allows us to confront a very difficult problem like this with some confidence

problem like this with some confidence

problem like this with some confidence so here this this was a six year old

so here this this was a six year old

so here this this was a six year old girl who had headaches she gets a scan

girl who had headaches she gets a scan

girl who had headaches she gets a scan and she had this as you can see in the

and she had this as you can see in the

and she had this as you can see in the middle that bright areas is a brain

middle that bright areas is a brain

middle that bright areas is a brain tumor within within the very deepest

tumor within within the very deepest

tumor within within the very deepest reaches of her brain and so we had a

reaches of her brain and so we had a

reaches of her brain and so we had a real challenge how do we get to that

real challenge how do we get to that

real challenge how do we get to that this needs to be removed she’s suffering

this needs to be removed she’s suffering

this needs to be removed she’s suffering symptoms and so with those tools with

symptoms and so with those tools with

symptoms and so with those tools with those maps we were able to sneak in in

those maps we were able to sneak in in

those maps we were able to sneak in in between the two halves of the brain and

between the two halves of the brain and

between the two halves of the brain and minimally disrupt the brain so as to

minimally disrupt the brain so as to

minimally disrupt the brain so as to remove that person that person’s tumor

remove that person that person’s tumor

remove that person that person’s tumor and they woke up beautifully after the

and they woke up beautifully after the

and they woke up beautifully after the operation and everyone was relieved and

operation and everyone was relieved and

operation and everyone was relieved and we were all feeling very good about what

we were all feeling very good about what

we were all feeling very good about what we were able to do with our hands with

we were able to do with our hands with

we were able to do with our hands with this great technology but the problem

this great technology but the problem

this great technology but the problem with brain tumors is this is that they

with brain tumors is this is that they

with brain tumors is this is that they come back and so unfortunately this

come back and so unfortunately this

come back and so unfortunately this person’s tumor came back several years

person’s tumor came back several years

person’s tumor came back several years later and it came back in a way that

later and it came back in a way that

later and it came back in a way that surgery no longer had a role and so

surgery no longer had a role and so

surgery no longer had a role and so first as a as a clinician and with this

first as a as a clinician and with this

first as a as a clinician and with this knowledge cancer is a leading cause of

knowledge cancer is a leading cause of

knowledge cancer is a leading cause of non accidental death and Canadian and

non accidental death and Canadian and

non accidental death and Canadian and American children and brain tumors

American children and brain tumors

American children and brain tumors represent many of these because other

represent many of these because other

represent many of these because other types of childhood cancers are being

types of childhood cancers are being

types of childhood cancers are being cured at a much higher rate for example

cured at a much higher rate for example

cured at a much higher rate for example childhood leukemia and so for myself

childhood leukemia and so for myself

childhood leukemia and so for myself being a brain surgeon and seeing wanting

being a brain surgeon and seeing wanting

being a brain surgeon and seeing wanting to always push myself to do better and

to always push myself to do better and

to always push myself to do better and to go beyond what I’d been taught I I

to go beyond what I’d been taught I I

to go beyond what I’d been taught I I wanted to do much more than that I

wanted to do much more than that I

wanted to do much more than that I didn’t want surgery to be the last step

didn’t want surgery to be the last step

didn’t want surgery to be the last step I wanted to understand more and for this

I wanted to understand more and for this

I wanted to understand more and for this we have to turn to biology what can be

we have to turn to biology what can be

we have to turn to biology what can be done what can be done in science and

done what can be done in science and

done what can be done in science and scientific research and this is really

scientific research and this is really

scientific research and this is really what our main problem is for a lot of

what our main problem is for a lot of

what our main problem is for a lot of cancers that affect many different

cancers that affect many different

cancers that affect many different systems in the human body or

systems in the human body or

systems in the human body or problem isn’t necessarily with with the

problem isn’t necessarily with with the

problem isn’t necessarily with with the for the first the first forays into

for the first the first forays into

for the first the first forays into treatment still surgery is a very

treatment still surgery is a very

treatment still surgery is a very important part of treatment of cancer in

important part of treatment of cancer in

important part of treatment of cancer in many different systems so it seems like

many different systems so it seems like

many different systems so it seems like such a crude act to physically remove

such a crude act to physically remove

such a crude act to physically remove but still today it’s still one of the

but still today it’s still one of the

but still today it’s still one of the most important things that needs to be

most important things that needs to be

most important things that needs to be done in order to treat a person’s cancer

done in order to treat a person’s cancer

done in order to treat a person’s cancer but the problem is with recurrence so

but the problem is with recurrence so

but the problem is with recurrence so recurrence after first treatment is a

recurrence after first treatment is a

recurrence after first treatment is a main obstacle to cure for many cancers

main obstacle to cure for many cancers

main obstacle to cure for many cancers including and especially brain cancer so

including and especially brain cancer so

including and especially brain cancer so one of the cancers that were very

one of the cancers that were very

one of the cancers that were very interested in which is quite common in

interested in which is quite common in

interested in which is quite common in young young people is a tumor called

young young people is a tumor called

young young people is a tumor called medulloblastoma and so I turn to

medulloblastoma and so I turn to

medulloblastoma and so I turn to thinking about well first what what do

thinking about well first what what do

thinking about well first what what do these tumors look like under a

these tumors look like under a

these tumors look like under a microscope and so this is a typical

microscope and so this is a typical

microscope and so this is a typical picture of a medulla blastoma where here

picture of a medulla blastoma where here

picture of a medulla blastoma where here purple is staining the nuclei and pink

purple is staining the nuclei and pink

purple is staining the nuclei and pink stains the cytoplasm of the cells and so

stains the cytoplasm of the cells and so

stains the cytoplasm of the cells and so here there are many cells packed

here there are many cells packed

here there are many cells packed together and essentially all of this

together and essentially all of this

together and essentially all of this looks quite similar all the cells

looks quite similar all the cells

looks quite similar all the cells morphologically look similar so I asked

morphologically look similar so I asked

morphologically look similar so I asked a question is that really true are those

a question is that really true are those

a question is that really true are those cells really truly the same and so we

cells really truly the same and so we

cells really truly the same and so we started to ask that question by staining

started to ask that question by staining

started to ask that question by staining tumors for different markers and we had

tumors for different markers and we had

tumors for different markers and we had a clue that cancer of the brain might be

a clue that cancer of the brain might be

a clue that cancer of the brain might be like an aberrant developmental process

like an aberrant developmental process

like an aberrant developmental process based on stem cells and I’ll come back

based on stem cells and I’ll come back

based on stem cells and I’ll come back to that more detail but so what we

to that more detail but so what we

to that more detail but so what we wanted to do and this this this was from

wanted to do and this this this was from

wanted to do and this this this was from a model of the same cancer that that can

a model of the same cancer that that can

a model of the same cancer that that can be modeled in an animal and we stained

be modeled in an animal and we stained

be modeled in an animal and we stained cells within that tumor with different

cells within that tumor with different

cells within that tumor with different markers and so these these are markers

markers and so these these are markers

markers and so these these are markers sox2 dcx and new end they represent

sox2 dcx and new end they represent

sox2 dcx and new end they represent markers of stem cells progenitor cells

markers of stem cells progenitor cells

markers of stem cells progenitor cells and mature cells of the normal brain and

and mature cells of the normal brain and

and mature cells of the normal brain and so we find these normal markers also in

so we find these normal markers also in

so we find these normal markers also in the tumor and this suggests that maybe

the tumor and this suggests that maybe

the tumor and this suggests that maybe there’s a relationship between those

there’s a relationship between those

there’s a relationship between those cells maybe this type of cancer

cells maybe this type of cancer

cells maybe this type of cancer represents an abnormal stem cell system

represents an abnormal stem cell system

represents an abnormal stem cell system and key point here is that the stem

and key point here is that the stem

and key point here is that the stem cells which expresses gene

cells which expresses gene

cells which expresses gene sox2 are relatively few but we think

sox2 are relatively few but we think

sox2 are relatively few but we think those are the key cells so we faced with

those are the key cells so we faced with

those are the key cells so we faced with that initial information we want to ask

that initial information we want to ask

that initial information we want to ask this question our relationships between

this question our relationships between

this question our relationships between stem cells and they’re more mature

stem cells and they’re more mature

stem cells and they’re more mature daughter cell progeny maintained in a

daughter cell progeny maintained in a

daughter cell progeny maintained in a cancer context and I’m going to show you

cancer context and I’m going to show you

cancer context and I’m going to show you tell you show you a little bit of some

tell you show you a little bit of some

tell you show you a little bit of some experiments that suggest that the answer

experiments that suggest that the answer

experiments that suggest that the answer to that is yes there’s a lot of

to that is yes there’s a lot of

to that is yes there’s a lot of excitement now over the last 20 years

excitement now over the last 20 years

excitement now over the last 20 years that our brain is more dynamic than we

that our brain is more dynamic than we

that our brain is more dynamic than we ever thought before because there are

ever thought before because there are

ever thought before because there are several regions in the brain where there

several regions in the brain where there

several regions in the brain where there are new neurons made in the brain that

are new neurons made in the brain that

are new neurons made in the brain that that may play a role in for example in

that may play a role in for example in

that may play a role in for example in memory formation in a part of the brain

memory formation in a part of the brain

memory formation in a part of the brain called the hippocampus which is on the

called the hippocampus which is on the

called the hippocampus which is on the inner part of the temporal lobe and

inner part of the temporal lobe and

inner part of the temporal lobe and perhaps making new neurons is essential

perhaps making new neurons is essential

perhaps making new neurons is essential to being able to generate new memories

to being able to generate new memories

to being able to generate new memories but so the stem cells reside within they

but so the stem cells reside within they

but so the stem cells reside within they generate other cells that amplify the

generate other cells that amplify the

generate other cells that amplify the number of cells because they divide

number of cells because they divide

number of cells because they divide frequently and ultimately they undergo a

frequently and ultimately they undergo a

frequently and ultimately they undergo a process called differentiation or

process called differentiation or

process called differentiation or maturation into cells that are neurons

maturation into cells that are neurons

maturation into cells that are neurons or glia which are astrocytes are oolagah

or glia which are astrocytes are oolagah

or glia which are astrocytes are oolagah dentro sites supporting cells for the

dentro sites supporting cells for the

dentro sites supporting cells for the neurons and so in the normal context

neurons and so in the normal context

neurons and so in the normal context during development that process works as

during development that process works as

during development that process works as a baby’s brain grows during development

a baby’s brain grows during development

a baby’s brain grows during development and there’s there’s more robust activity

and there’s there’s more robust activity

and there’s there’s more robust activity of that early on in life in humans and

of that early on in life in humans and

of that early on in life in humans and there’s that diminishes over time but in

there’s that diminishes over time but in

there’s that diminishes over time but in the normal context to make that

the normal context to make that

the normal context to make that beautiful brain that you saw those

beautiful brain that you saw those

beautiful brain that you saw those pictures of that these processes are

pictures of that these processes are

pictures of that these processes are extremely tightly regulated and are

extremely tightly regulated and are

extremely tightly regulated and are beautifully orchestrated and I like this

beautifully orchestrated and I like this

beautifully orchestrated and I like this image from one of my favorite records

image from one of my favorite records

image from one of my favorite records that that that illustrates the this

that that that illustrates the this

that that that illustrates the this process but in cancer we think all those

process but in cancer we think all those

process but in cancer we think all those there’s a resemblance to that those kind

there’s a resemblance to that those kind

there’s a resemblance to that those kind of relationships it’s now gone haywire

of relationships it’s now gone haywire

of relationships it’s now gone haywire but there are some clues within that

but there are some clues within that

but there are some clues within that tell us what we can do so another key

tell us what we can do so another key

tell us what we can do so another key point is cancers often represent

point is cancers often represent

point is cancers often represent distortions of our normal selves and to

distortions of our normal selves and to

distortions of our normal selves and to take that one step further in the brain

take that one step further in the brain

take that one step further in the brain is brain cancers represent a bear

is brain cancers represent a bear

is brain cancers represent a bear and developmental processes and brain

and developmental processes and brain

and developmental processes and brain cancers we think grow because they

cancers we think grow because they

cancers we think grow because they contain genetically abnormal stem cells

contain genetically abnormal stem cells

contain genetically abnormal stem cells that are our if you will on a misguided

that are our if you will on a misguided

that are our if you will on a misguided mission to grow abnormal brain tissue

mission to grow abnormal brain tissue

mission to grow abnormal brain tissue and so we need to understand that

and so we need to understand that

and so we need to understand that process and so I’m just going to show

process and so I’m just going to show

process and so I’m just going to show you one example of one experiment that

you one example of one experiment that

you one example of one experiment that supports this idea and it’s it’s a

supports this idea and it’s it’s a

supports this idea and it’s it’s a classical experiment that that

classical experiment that that

classical experiment that that scientists who are interested in

scientists who are interested in

scientists who are interested in development of tissues does it’s

development of tissues does it’s

development of tissues does it’s something called a lineage trace and

something called a lineage trace and

something called a lineage trace and it’s a definitive measurement of the

it’s a definitive measurement of the

it’s a definitive measurement of the potency of a cell that’s marked in a

potency of a cell that’s marked in a

potency of a cell that’s marked in a tissue and it tells us whether how well

tissue and it tells us whether how well

tissue and it tells us whether how well that tissue can replenish and how how

that tissue can replenish and how how

that tissue can replenish and how how that tissue matures and we wanted to ask

that tissue matures and we wanted to ask

that tissue matures and we wanted to ask this question

this question

this question those five percents those few little

those five percents those few little

those five percents those few little green cells I showed you in that picture

green cells I showed you in that picture

green cells I showed you in that picture that expressed this gene key gene called

that expressed this gene key gene called

that expressed this gene key gene called sox2 could those cells be at the roots

sox2 could those cells be at the roots

sox2 could those cells be at the roots of growth of this type of childhood

of growth of this type of childhood

of growth of this type of childhood tumor and so a graduate student in my

tumor and so a graduate student in my

tumor and so a graduate student in my lab robert van ER did the experiment it

lab robert van ER did the experiment it

lab robert van ER did the experiment it was a very difficult experiment but what

was a very difficult experiment but what

was a very difficult experiment but what he was able to do is he could we used a

he was able to do is he could we used a

he was able to do is he could we used a genetic trick that was embedded into

genetic trick that was embedded into

genetic trick that was embedded into animals that would that would grow up

animals that would that would grow up

animals that would that would grow up medulloblastoma naturally and this model

medulloblastoma naturally and this model

medulloblastoma naturally and this model is very close to the to the sharing the

is very close to the to the sharing the

is very close to the to the sharing the same genetic changes in the same the

same genetic changes in the same the

same genetic changes in the same the tumors look the same as the human tumors

tumors look the same as the human tumors

tumors look the same as the human tumors they express the same abnormal genetic

they express the same abnormal genetic

they express the same abnormal genetic programs as a human tumor so we thought

programs as a human tumor so we thought

programs as a human tumor so we thought it was it was a terrific model and here

it was it was a terrific model and here

it was it was a terrific model and here was something that you actually can’t do

was something that you actually can’t do

was something that you actually can’t do in a human being but you can do in a

in a human being but you can do in a

in a human being but you can do in a very good animal model so what Robert

very good animal model so what Robert

very good animal model so what Robert was able to do is he could mark the Sox

was able to do is he could mark the Sox

was able to do is he could mark the Sox to positive cells and show initially

to positive cells and show initially

to positive cells and show initially that these were few cells in the tumor

that these were few cells in the tumor

that these were few cells in the tumor and then what we did is we followed that

and then what we did is we followed that

and then what we did is we followed that tumor over time to trace the progeny of

tumor over time to trace the progeny of

tumor over time to trace the progeny of these mark cells and essentially what

these mark cells and essentially what

these mark cells and essentially what happens here is that cell becomes

happens here is that cell becomes

happens here is that cell becomes acquires a color core this red color

acquires a color core this red color

acquires a color core this red color when that cell divided and generated two

when that cell divided and generated two

when that cell divided and generated two daughter cells both the daughter cells

daughter cells both the daughter cells

daughter cells both the daughter cells became red and then as they divided both

became red and then as they divided both

became red and then as they divided both their daughter cells become red and over

their daughter cells become red and over

their daughter cells become red and over time we wanted to watch to see if the

time we wanted to watch to see if the

time we wanted to watch to see if the tumor turn

tumor turn

tumor turn red and essentially and here’s the real

red and essentially and here’s the real

red and essentially and here’s the real experiment it shows that the tumor grows

experiment it shows that the tumor grows

experiment it shows that the tumor grows based on the division and multiplication

based on the division and multiplication

based on the division and multiplication of a rare population of cells that

of a rare population of cells that

of a rare population of cells that reside within strongly supporting that

reside within strongly supporting that

reside within strongly supporting that this this type of tumor is driven in a

this this type of tumor is driven in a

this this type of tumor is driven in a based on an aberrant stem cell system so

based on an aberrant stem cell system so

based on an aberrant stem cell system so on the right you can see over several

on the right you can see over several

on the right you can see over several weeks the tumor essentially turns red

weeks the tumor essentially turns red

weeks the tumor essentially turns red and it came from few cells so these

and it came from few cells so these

and it came from few cells so these cells we think are at the root of the

cells we think are at the root of the

cells we think are at the root of the growth of this kind of cancer and the

growth of this kind of cancer and the

growth of this kind of cancer and the key thing here is we then started to

key thing here is we then started to

key thing here is we then started to test conventional treatments in in in

test conventional treatments in in in

test conventional treatments in in in this model to see how do the

this model to see how do the

this model to see how do the conventional treatments target these

conventional treatments target these

conventional treatments target these different cell types in these in these

different cell types in these in these

different cell types in these in these tumors and essentially what we found

tumors and essentially what we found

tumors and essentially what we found here is that the usual treatments were

here is that the usual treatments were

here is that the usual treatments were were fantastic at killing a lot of the

were fantastic at killing a lot of the

were fantastic at killing a lot of the cells in the tumor we found good drugs

cells in the tumor we found good drugs

cells in the tumor we found good drugs already that also work in patients that

already that also work in patients that

already that also work in patients that are very good at at shrinking these

are very good at at shrinking these

are very good at at shrinking these tumors and and improving the symptoms

tumors and and improving the symptoms

tumors and and improving the symptoms but but what you may not be able to see

but but what you may not be able to see

but but what you may not be able to see so well here but on the right is after

so well here but on the right is after

so well here but on the right is after the treatment we see more red cells in

the treatment we see more red cells in

the treatment we see more red cells in this tumor and what that means is that

this tumor and what that means is that

this tumor and what that means is that the we spared a population of cells

the we spared a population of cells

the we spared a population of cells we’re leaving something behind we’re

we’re leaving something behind we’re

we’re leaving something behind we’re leaving a reservoir of cells behind that

leaving a reservoir of cells behind that

leaving a reservoir of cells behind that may show the capacity to regrow the

may show the capacity to regrow the

may show the capacity to regrow the tumor and and so in applying the stem

tumor and and so in applying the stem

tumor and and so in applying the stem cell biology approach this developmental

cell biology approach this developmental

cell biology approach this developmental framework if you will to thinking about

framework if you will to thinking about

framework if you will to thinking about how cancer grows we can start to divide

how cancer grows we can start to divide

how cancer grows we can start to divide up different cell types in the tumor in

up different cell types in the tumor in

up different cell types in the tumor in two distinct compartments I’m not going

two distinct compartments I’m not going

two distinct compartments I’m not going to go over all of this but essentially

to go over all of this but essentially

to go over all of this but essentially there are a few cells that are that have

there are a few cells that are that have

there are a few cells that are that have a stem cell property that actually

a stem cell property that actually

a stem cell property that actually another key point about those cells is

another key point about those cells is

another key point about those cells is that they’re very slowly dividing they

that they’re very slowly dividing they

that they’re very slowly dividing they and our general treatments for cancer

and our general treatments for cancer

and our general treatments for cancer are very good at targeting cells that

are very good at targeting cells that

are very good at targeting cells that are rapidly dividing we figure that

are rapidly dividing we figure that

are rapidly dividing we figure that process out but we haven’t figured out

process out but we haven’t figured out

process out but we haven’t figured out so well how to deal with cells that are

so well how to deal with cells that are

so well how to deal with cells that are lurking within the cancer that maybe

lurking within the cancer that maybe

lurking within the cancer that maybe have a very slow dividing

have a very slow dividing

have a very slow dividing potential seems like the drugs that we

potential seems like the drugs that we

potential seems like the drugs that we have don’t target these slowly cycling

have don’t target these slowly cycling

have don’t target these slowly cycling cells those cells in turn generates

cells those cells in turn generates

cells those cells in turn generates progeny that divide fast which are

progeny that divide fast which are

progeny that divide fast which are cancer progenitors which respond to

cancer progenitors which respond to

cancer progenitors which respond to chemotherapy which we can wipe out and

chemotherapy which we can wipe out and

chemotherapy which we can wipe out and eventually those cells undergo a

eventually those cells undergo a

eventually those cells undergo a maturation process not like the normal

maturation process not like the normal

maturation process not like the normal brain but still resembling the normal

brain but still resembling the normal

brain but still resembling the normal brain but these cells that mature

brain but these cells that mature

brain but these cells that mature actually are short live and are

actually are short live and are

actually are short live and are eliminated and although they form a

eliminated and although they form a

eliminated and although they form a component of the mass of the tumor which

component of the mass of the tumor which

component of the mass of the tumor which can cause symptoms they actually

can cause symptoms they actually

can cause symptoms they actually disappear over time they’re programmed

disappear over time they’re programmed

disappear over time they’re programmed to disappear and it may be analogous to

to disappear and it may be analogous to

to disappear and it may be analogous to what also happens in the developing

what also happens in the developing

what also happens in the developing brain we during development we generate

brain we during development we generate

brain we during development we generate way way more neurons than we need and as

way way more neurons than we need and as

way way more neurons than we need and as those neurons start to make connections

those neurons start to make connections

those neurons start to make connections a lot of the extra neurons are pruned so

a lot of the extra neurons are pruned so

a lot of the extra neurons are pruned so we there may be this process is also

we there may be this process is also

we there may be this process is also being recapitulated in this cancer

being recapitulated in this cancer

being recapitulated in this cancer context but what this tells us also is

context but what this tells us also is

context but what this tells us also is that we need different types of

that we need different types of

that we need different types of treatments for these different types of

treatments for these different types of

treatments for these different types of cells and applying the stem cell

cells and applying the stem cell

cells and applying the stem cell thinking means we don’t we not we not

thinking means we don’t we not we not

thinking means we don’t we not we not only have to target the fast awaiting

only have to target the fast awaiting

only have to target the fast awaiting cells we need something that targets the

cells we need something that targets the

cells we need something that targets the slow dividing cells or maybe what we

slow dividing cells or maybe what we

slow dividing cells or maybe what we should do is just force all of these

should do is just force all of these

should do is just force all of these cells to mature into these

cells to mature into these

cells to mature into these differentiated cell types and then those

differentiated cell types and then those

differentiated cell types and then those cells what cells will have a limited

cells what cells will have a limited

cells what cells will have a limited lifespan and will disappear so I think

lifespan and will disappear so I think

lifespan and will disappear so I think one of the key points I want to get

one of the key points I want to get

one of the key points I want to get across today and I think it applies

across today and I think it applies

across today and I think it applies generally to cancer is not every cancer

generally to cancer is not every cancer

generally to cancer is not every cancer is functionally created equal even if

is functionally created equal even if

is functionally created equal even if they may have the same genetic changes

they may have the same genetic changes

they may have the same genetic changes they’re not behaving the same way and we

they’re not behaving the same way and we

they’re not behaving the same way and we need to figure that out so cancer is

need to figure that out so cancer is

need to figure that out so cancer is much more than genetic mutations genetic

much more than genetic mutations genetic

much more than genetic mutations genetic mutations are essential to get cancer

mutations are essential to get cancer

mutations are essential to get cancer growing are essential to be cancer but

growing are essential to be cancer but

growing are essential to be cancer but but it’s how those genetic changes are

but it’s how those genetic changes are

but it’s how those genetic changes are being used by the cells that also

being used by the cells that also

being used by the cells that also dictates the way that cancer behaves so

dictates the way that cancer behaves so

dictates the way that cancer behaves so we think that cancer reflects how

we think that cancer reflects how

we think that cancer reflects how genetic changes shape the behavior of

genetic changes shape the behavior of

genetic changes shape the behavior of normal tissue growth and regenerative

normal tissue growth and regenerative

normal tissue growth and regenerative processes and in our in our group we’ve

processes and in our in our group we’ve

processes and in our in our group we’ve identified a cellular target in

identified a cellular target in

identified a cellular target in medulloblastoma

medulloblastoma

medulloblastoma and also in glioblastoma of adults and

and also in glioblastoma of adults and

and also in glioblastoma of adults and we’re starting to characterize more of

we’re starting to characterize more of

we’re starting to characterize more of the programs that dictate the behavior

the programs that dictate the behavior

the programs that dictate the behavior of those cells and we think that we have

of those cells and we think that we have

of those cells and we think that we have the cell in hand that is responsible for

the cell in hand that is responsible for

the cell in hand that is responsible for the root growth of these tumors but also

the root growth of these tumors but also

the root growth of these tumors but also responsible for the recurrence having

responsible for the recurrence having

responsible for the recurrence having these cells at hand

these cells at hand

these cells at hand gives us the chance to discover new

gives us the chance to discover new

gives us the chance to discover new therapies that may more that may better

therapies that may more that may better

therapies that may more that may better affect long lasting cures so I think

affect long lasting cures so I think

affect long lasting cures so I think there is hope for a better future for

there is hope for a better future for

there is hope for a better future for for children and adults with brain

for children and adults with brain

for children and adults with brain cancer based on applying this kind of

cancer based on applying this kind of

cancer based on applying this kind of framework to understanding brain cancer

framework to understanding brain cancer

framework to understanding brain cancer and it and really as someone who started

and it and really as someone who started

and it and really as someone who started off as a clinician as a surgeon I love

off as a clinician as a surgeon I love

off as a clinician as a surgeon I love what I do in looking after a patient’s

what I do in looking after a patient’s

what I do in looking after a patient’s and being able to use my hands and to be

and being able to use my hands and to be

and being able to use my hands and to be able to have a dramatic impact on

able to have a dramatic impact on

able to have a dramatic impact on someone’s life

someone’s life

someone’s life with an operation but I recognize that

with an operation but I recognize that

with an operation but I recognize that still there’s limitations in what we can

still there’s limitations in what we can

still there’s limitations in what we can do with our hands and I think we’re not

do with our hands and I think we’re not

do with our hands and I think we’re not we’re not yet to be replaced by robots

we’re not yet to be replaced by robots

we’re not yet to be replaced by robots because still there’s aspects of the

because still there’s aspects of the

because still there’s aspects of the human motor and sensory systems that

human motor and sensory systems that

human motor and sensory systems that still can’t be replaced by robots so we

still can’t be replaced by robots so we

still can’t be replaced by robots so we need surgeons but we need much more than

need surgeons but we need much more than

need surgeons but we need much more than surgery we need to understand biology

surgery we need to understand biology

surgery we need to understand biology and I think the key for for young people

and I think the key for for young people

and I think the key for for young people is science Canada and the world needs

is science Canada and the world needs

is science Canada and the world needs more people engaged in scientific

more people engaged in scientific

more people engaged in scientific research to ask creative original

research to ask creative original

research to ask creative original questions and to think outside the box

questions and to think outside the box

questions and to think outside the box we think in a way we thought outside of

we think in a way we thought outside of

we think in a way we thought outside of the box and look and looking at brain

the box and look and looking at brain

the box and look and looking at brain cancer this way and we’re very hopeful

cancer this way and we’re very hopeful

cancer this way and we’re very hopeful what that might mean for the future

what that might mean for the future

what that might mean for the future thank you very much for your attention

thank you very much for your attention

thank you very much for your attention [Applause]